T-cell signature cytokines distinguish pulmonary sarcoidosis from pulmonary tuberculosis

Sarcoidosis is a systemic inflammatory disorder characterized by tissue infiltration due to mononuclear phagocytes and lymphocytes and associated noncaseating granuloma formation. Pulmonary sarcoidosis (PS) shares a number of clinical, radiological, and histopathological characteristics with that of pulmonary tuberculosis (PTB). Due to this, clinicians face issues in differentiating between PS and PTB in a substantial number of cases. There is a lack of any specific biomarker that can diagnose PS distinctively from PTB. We compared T-cell-based signature cytokines in patients with PS and PTB. In this study, we proposed a serum biomarker panel consisting of cytokines from cells: T helper (Th) 1 [interferon-gamma (IFN-γ); tumor necrosis factor-alpha (TNF-α)], Th9 [interleukin (IL)-9], Th17 [IL-17], and T regulatory (Treg) [IL-10; transforming growth factor-beta (TGF-β)]. We performed the principal component analysis that demonstrated that our serum cytokine panel has a significant predictive ability to differentiate PS from PTB. Our results could aid clinicians to improve the diagnostic workflow for patients with PS in TB endemic settings where the diagnosis between PS and PTB is often ambiguous.     

Daily variability in resting levels of cardiovascular variables in normal subjects and those with homozygous sickle cell disease

Measurements were made of cardiovascular variables and oral temperature in 16 male subjects with homozygous sickle cell disease (SS) and in 17 matched controls (AA) at 10.00 a.m., 1.00 p.m. and 4.00 p.m. All subjects were in a rested state throughout. At 10.00 a.m., mean arterial pressure was lower, while heart rate, total forearm blood flow and cutaneous red cell flux in the forearm were higher in SS than AA. Vascular resistance in total forearm and forearm skin, calculated by dividing arterial pressure by blood flow or red cell flux, were lower in SS but hand cutaneous red cell flux and vascular resistance were not significantly different in SS and AA. In both SS and AA, there were parallel increases over the three sessions, in mean arterial pressure (by 12 and 10%, respectively) forearm vascular resistance (by 17 and 27%) and hand cutaneous vascular resistance and hand cutaneous resistance (by 240 and 350%) whereas forearm blood flow and hand cutaneous red cell flux fell. By contrast, forearm cutaneous resistance showed no change during the day in SS, but increased progressively in AA (by 75%). These results indicate that, during the day, there is progressive vasoconstriction in forearm muscle and hand skin in SS and AA and also in forearm skin of AA that contributes to a progressive rise in the resting level of mean arterial pressure. We suggest this daily variability should be considered in studies of cardiovascular function: within a given study they should be performed at the same time of day.     

Mycotic keratitis in non-steroid exposed vernal keratoconjunctivitis.

PURPOSE: To report a patient with vernal keratoconjunctivitis who developed mycotic keratitis in absence of known risk factors. METHODS: A 17-year-old male suffering from vernal keratoconjunctivitis presented with infective keratitis. The patient had been treated in the past with topical antihistaminics and vasoconstrictors. The patient had not been exposed to topical steroids in 2 years of follow-up. He did not have dry eye or corneal micro or macroerosions prior to the development of infective keratitis. Corneal scrapings were obtained and subjected to KOH wet mount smear, calcofluor and Grams stain as well as bacterial culture sensitivity and fungal culture. RESULTS: Clinical diagnosis of mycotic keratitis in association with vernal conjunctivitis was supported by microbiological investigations. KOH wet mount and calcofluor staining showed presence of filamentous septate hyphae while fungal culture showed growth of aspergillus fumigatus. Antifungal therapy was initiated in the form of topical natamycin 5% suspension to which the patient responded and recovered 6/6 final visual acuity. CONCLUSION: The authors wish to conclude that patients suffering from vernal keratoconjunctivitis, even in the absence of corneal involvement, steroid exposure and trauma, may be at increased risk of developing keratomycosis.     

Sperm Quality Improvement in Cryopreserved Human Semen

Purpose

We determined if separation of spermatozoa (washed) on a discontinuous colloidal suspension of silica (Percoll^†) density gradient before cryopreservation improves post-thaw motility compared to an unprocessed (raw) cryopreserved sample.

Materials and Methods

Ten normal healthy volunteers recruited into the andrology laboratory donor program were studied. Raw and washed cryopreserved spermatozoa were compared for loss of motility with time, motion characteristics, viability and membrane integrity after incubation for 1, 6 and 24 hours. Within group comparisons were made to baseline measurements (0 hours before incubation).

Results

Raw and washed cryopreserved spermatozoa showed statistically significant decreases in motility and other motion characteristics after thawing. There were significant decreases in motility and other motion characteristics after incubation periods of 1, 6 and 24 hours, and significant decreases in viability and membrane integrity at 6 and 24 hours in the unprocessed spermatozoa. Although, motility and motion characteristics of washed samples decreased significantly with longer incubation periods, loss of motility with time (longevity) was greater in raw samples. Washed samples retained greater sperm motility for up to 24 hours (p less than 0.03).

Conclusions

Specimens prepared by Percoll separation techniques before freezing offer the possibility of selecting spermatozoa that retain motility for up to 24 hours. This finding can be of benefit for couples undergoing intrauterine insemination to achieve pregnancy.     

Pharmacokinetics of methotrexate in leukemia cells: Effect of dose and mode of injection

A lumped compartmental model has been derived to predict methotrexate concentration as a function of time for L1210 cells in BD2F ₁ female mice at doses ranging from 3 mg/kg to 400 mg/kg. Using standard methods of parameter estimation as well as experimental determinations, an integrated approach was derived to account for the differences between the subcutaneous (s.c.) and intraperitoneal (i.p.) modes of injection. It was found that a single generalized forcing function can be used to fit plasma concentration after s.c. injection for all doses. Adequate fits (average error<20% while the standard deviation of experimental determinations was±22%) of L1210 cell data after s.c. injection were obtained. The best results were for a maximum facilitated influx constant V_max of 0.424 g/min/ml, a Michaelis influx constant K_m of 1,42 g/ml, and a first-order efflux constant of 0.047 min^–1.The model simulations were not sensitive to V_max, K_m,and so long as the ratio V_max/was approximately 9g/ml. The values of V _max ,K _m ,and which were obtained from our analysis of the in vivodata can be explained on the basis of previously performed in vitroexperiments. The parameters obtained from modeling the s.c. data were then applied for i.p. injection data. The resulting fits were adequate (average error<20% while the standard deviation of experimental determinations was±22%). A single generalized forcing function for drug concentration in the peritoneal cavity after i.p. injection for all doses was derived. The application of these results enables the prediction of methotrexate concentration in neoplastic cells at other doses after either s.c. or i.p. injection.     

5-Hydroxytryptamine-induced increase in left ventricular dP/dtmax does not suggest the presence of ventricular 5-HT4 receptors in the pig

Summary Although 5-hydroxytryptamine (5-HT) increases porcine atrial force and rate via 5-HT₄ receptors, its effect on left ventricular contractility is not known. Therefore, using the maximum rate of rise of left ventricular pressure (LVdP/dt_max) as an index of cardiac contractility, we have attempted to analyze the possible role of ventricular 5-HT₄ receptors in the anaesthetized pig. The full agonists at 5-HT₄ receptors, 5-HT and 5-methoxytryptamine (each 3, 10 and 30 g · kg^–1), and the -adrenoceptor agonist, isoprenaline (0.01, 0.03 and 0.1 g · kg^–1), increased heart rate, LVdP/dt_max and cardiac output. For a given degree of tachycardia, the increase in LVdP/dt_max by isoprenaline was substantially more than that observed with either 5-HT or 5-methoxytryptamine. The 5-HT₄ receptor partial agonist, renzapride (3, 10, 30, 100 and 300 g · kg^–1), also increased heart rate and LVdP/dt_max dose-dependently. When the heart was paced at 150 beats · min^–1, increases in LVdP/dt_max as well as cardiac output (except with the highest doses) by 5-HT, 5-methoxytryptamine and isoprenaline were clearly attenuated. However, the magnitude of attenuation of LVdP/dt_max responses by cardiac pacing was more marked in the case of 5-HT and 5-methoxytryptamine than with isoprenaline.The effects of renzapride (300 g · kg^–1) and tropisetron (0.3 and 3 mg · kg^–1) on increases in heart rate and LVdP/dt_max by 5-HT, 5-methoxytryptamine and isoprenaline were also studied. In the absence of atrial pacing, both renzapride and tropisetron (3 mg · kg^–1) effectively antagonized the responses to 5-HT and 5-methoxytryptamine; except for some decrease in the LVdP/dt_max response by tropisetron, the effect of isoprenaline remained essentially unchanged after the antagonists. During atrial pacing, renzapride significantly antagonized the responses to the first two doses of 5-HT, but the responses to the highest 5-HT dose and to 5-methoxytryptamine remained unaffected. Though, particularly after its higher dose, tropisetron reduced the responses to 5-HT and 5-methoxytryptamine, isoprenaline responses were also affected.The above results show that a significant part of the increase in LVdP/dt_max by 5-HT receptor agonists in the anaesthetized pig is a consequence of tachycardia elicited by these compounds via 5-HT₄ receptors. Since the increase in LVdP/dt_max, compared to tachycardia, was much less with 5-HT and 5-methoxytryptamine than with isoprenaline, and since the antagonism by renzapride and tropisetron against 5-HT and 5-methoxytryptamine during atrial pacing was relatively weaker and/or unspecific, it appears unlikely that the increase in LVdP/dt_max, during atria] pacing is mediated by ventricular 5-HT₄ receptors. This view is substantiated by our recent in vitro experiments where 5-HT (0.01 to 100 mol/l) failed to significantly increase contractions of porcine left ventricular trabeculae.Correspondence to P. R. Saxena at the above address     

Effects of Nd-YAG laser on platelet function in vitro: A comparative study using the spectraprobe, ‘hot tip’ and bare fibres

The effects of Nd-YAG laser irradiation on platelet function in vitro were studied using platelet rich plasma obtained from the blood of healthy volunteers. Laser delivery was effected via the bare optical fibre, thermal hot tip fibre and spectraprobe and the effects of these probes on platelet function were compared. Fall in platelet count and mean platelet volume (MPV) were proportional to increasing energy delivery with all three probes, the effect being maximal with the spectraprobe, moderate with the hot tip and least with the bare optical fibre. A significant decrease in percentage aggregation of platelets in response to added ADP, collagen and ristocetin with increasing energy delivery was also observed with all three probes. The formation of preformed aggregates, however, showed an increase proportional to energy delivery with all three probes.The differential effects of the various probes used in this study on platelet function may enhance our understanding of the complex role played by platelets in the pathogenesis of complications such as arterial thrombosis and re-occlusion after laser angioplasty.     

Unusual presentation of a giant glomus tumor

Giant glomus tumors pose a challenge to the Otologist by virtue of their location and vascularity. A vast majority of them present with tinnitus, conductive hearing loss and cranial nerve palsies. We report the case of a 16-year-old male patient who presented with sudden right-sided sensorineural hearing loss. This is an unusual presentation of a giant glomus tumor. We present the clinical features and management of this unusual case.     

Development of standard therapeutic guidelines for selected common diseases for the primary health care centres of a South Indian district

Method A questionnaire survey of medical officers was conducted to collect data on the most commonly‐presenting diseases and doctors' treatment choices in PHCs in Mysore. Draft guidelines were developed for these conditions based on available literature, together with microbiological sensitivity data from the three district hospitals. User feedback on the draft guidelines and on guidelines in general was obtained from medical officers using a postal questionnaire. Objective To develop standard therapeutic guidelines for selected common diseases for the primary health care centres (PHCs) of a South Indian district and to evaluate medical officers' perceptions about the proposed guidelines and about guidelines in general. Setting Sample of 17 of the 93 PHCs in Mysore. Key findings Upper respiratory tract infection was the most commonly‐presenting condition. Procaine penicillin was the most commonly‐used drug and there were examples of inappropriate treatment choices. The survey produced evidence that access to medicines on the government's “essential” list was not uniform, with many patients having to purchase prescribed drugs that were not on the list. The response rate to the user feedback questionnaire was 62 per cent (31 doctors). The medical officers had positive opinions about guidelines in general and felt that the guidelines we proposed were useful and would help them to improve their prescribing habits. Conclusions Prescribing in primary care in India needs to be improved. The involvement of potential users of the guidelines in their development should increase their acceptability and thus their use in practice.