Partnering for rotavirus vaccine introduction in India: A retrospective analysis.

BACKGROUND: The pre-existing partner network created in India for the delivery of polio vaccines was initially used to eradicate polio and later on embedded in the health systems network to promote routine immunization and other health interventions efficiently. The experience from this network offered lessons for strengthening the health care systems and provided a well-established network that could be utilized for other vaccine initiatives. It has also been established that successful partnerships between a broad range of stakeholders provide support, strengthen the health system, and accelerate vaccine innovation, introduction, access, logistics, and communication support. However, beyond polio eradication, there have not been too many documented success stories of vaccine introduction, which could be replicated in other new vaccine introductions and allied health initiatives. The authors have reviewed the successful and time-bound introduction of rotavirus vaccine (RVV) in India in the present article. METHODS: The review was conducted based on a partnership framework which analysed multiple factors-partnership prerequisites, partnership model, partnership process, and partnership performance, thereby providing a comprehensive insight into the successful utilization of partnership networks for rotavirus vaccine introduction under the Universal Immunization Program in India. RESULTS & CONCLUSION: The review also highlights the role of a lead agency in creating a fertile ground for lush, efficient, and effective partnerships amongst different stakeholders. The already existing RVV partnership framework reviewed by the authors can be successfully utilized for future new vaccine introductions.

Mycobacterium kansasii osteomyelitis presenting as a solitary lytic lesion of the ulna: fine-needle aspiration findings and morphologic comparison with other mycobacteria.

A 35-yr-old woman, with acquired immunodeficiency syndrome, presented with right arm pain, erythema, and swelling. A lytic lesion of the ulna was found by radiograph. Ultrasonic and fluoroscopic guided fine-needle aspiration (FNA) yielded a neutrophilic and histiocytic exudate admixed with abundant long, bacillary forms that appeared as negative images on Papanicolaou stain and as very coarsely beaded acid-fast bacilli, resembling candy canes, on Kinyoun stain. These morphologic features permitted a preliminary diagnosis of mycobacteriosis, possibly of M. kansasii (MK) etiology. Appropriate therapy was initiated and resulted in not only marked symptomatic improvement of osteomyelitis and cellulitis, but resolution of chronic pulmonary infiltrates, presumed to be caused by fibrosis. Culture confirmed MK infection 3 wk after FNA. MK is one of the few mycobacteria that has a sufficiently characteristic morphology to permit presumptive diagnosis by smear. Culture, however, still remains the definitive method of speciation.

Results of a study to correlate serum prostate specific antigen and reproductive hormone levels in patients with localized prostate cancer.

This cross-sectional study was undertaken to determine whether serum hormones (free testosterone, androstenedione, luteinizing hormone, or prolactin) have any influence on serum prostate specific antigen (PSA) levels in patients with stage A-C prostate cancer. Blood samples were collected prior to any treatment in 36 patients; in 19 (group 1), three blood samples were collected 10 minutes apart between 9:00 AM and 9:30 AM for each patient and pooled together to avoid diurnal and episodic variation in serum testosterone values. In the remaining patients, only one sample could be collected (group 2). Free testosterone, androstenedione, luteinizing hormone, prolactin, and PSA levels were determined with appropriate radioimmunoassay techniques. Statistical analyses were performed separately for groups 1 and 2, and then with pooled data. None of the hormones in any of the analyses showed any association to serum PSA values except for prolactin for the pooled data and for group 2. This statistical significance for prolactin disappeared on multivariate analysis. There were 21 African-American men and 15 whites in the study; no racial differences in hormonal levels were found except for lower luteinizing hormone levels in African Americans in group 2 and pooled data. No differences were found between group 1 and group 2 in the mean serum prolactin and luteinizing hormone values. Serum free testosterone, androstenedione, and luteinizing hormone appeared to have no influence on serum PSA values in nonmetastatic cancer patients. Serum prolactin values were inversely associated with PSA values in univariate analysis for the pooled data; this disappeared in multivariate analysis. Unlike other studies that found higher serum testosterone levels in African-American college students than whites, no such differences were seen in this age group. Luteinizing hormone was lower in African-American men than in whites in the pooled study population. Further studies are needed to clarify our findings.

Temporal (circadian) and functional relationship between prostate-specific antigen and testosterone in healthy men.

OBJECTIVES: To study the circadian relationship between serum prostate-specific antigen (PSA) and total testosterone in men without clinically evident prostate disease. METHODS: Blood samples were collected every 3 hours for 24 hours (eight per subject) from 11 clinically healthy men, ages 46 to 72 years. PSA was also monitored once a week for 6 weeks in 16 additional healthy men. PSA, testosterone, and age were correlated by linear regression, and 3-hourly PSA and testosterone values normalized to percent of individual mean were analyzed for circadian rhythm by the least squares fit of a 24-hour cosine. RESULTS: Mean PSA correlated positively (P < 0.001) and testosterone correlated negatively (P = 0.014) with age and inversely with each other (P < 0.001). The mean circadian range of change (ROC) from lowest to highest values for PSA was 0.37 +/- 0.07 ng/mL (28 +/- 9%), and for testosterone it was 202 +/- 23 ng/dL (53 +/- 7%). The mean ROC over 6 weeks was 0.32 +/- 0.04 ng/mL. A significant circadian rhythm was found for PSA (P = 0.011, amplitude = 5.4 +/- 1.8%, acrophase = 5:02 AM; 95% limits, 2:40 to 7:24 PM) and testosterone (P < 0.001, amplitude = 9.4 +/- 1.8%, acrophase = 8:38 AM; 95% limits, 7:12 to 10:04 AM). CONCLUSIONS: The temporal relationship between circadian rhythms in PSA and testosterone suggests different physiologic states over the 24 hours, which may be of chronopharmacologic interest with regard to dosing time of drugs or hormonal treatments intended to affect prostate growth and function. Within-day variation in PSA is of little diagnostic significance and does not prevent accurate clinical classification when a single specimen is used.

Measurement of weekly prostate specific antigen levels in patients receiving pelvic radiotherapy for nonprostatic malignancies.

PURPOSE: To study the response of nonmalignant prostatic tissue to ionizing irradiation in terms of the resultant changes in serum prostate specific antigen (PSA) levels. METHODS AND MATERIALS: Weekly serum PSA values were determined during radiotherapy (RT) in nine patients ("treatment group") without clinical evidence of prostate cancer (PC), and who received pelvic RT for other indications. Slopes for the rate of change in PSA was determined using model: log PSA = beta 0 + beta 1*week + beta 2*week2 + error. These results are compared with 17 normal volunteers ("control group") who were not exposed to ionizing irradiation. An attempt is made to compare any similarities and differences in subsets of 64 T1-T4N0M0 PC patients who received pelvic RT. RESULTS: An elevation in the serum PSA levels were noted in eight of nine patients in the "treatment group" with a median time of 4.2 weeks to reach the maximum serum PSA values. After an initial increase, PSA values declined. In some patients, manifold increase in PSA was noted, for example, from 1.8 to 13.5 ng/ml and 3.3 to 9.8 ng/ml in two patients. The PSA increase ranged from 50-650%. The median slope was 0.601 week-1 (range 0.192-3.045 week-1). No such increases were seen in the "control group" (median slope = 0.03 week-1; range, 0.18-0.13 week-1). When differences between the mean increase/decrease for each week compared to pretreatment values were analyzed, the irradiated group had statistically significant elevations in the PSA for weeks 3 (p = 0.034), 4 (p = 0.035), and 5 (p = 0.024). A similar trend of increasing PSA levels during radiotherapy was noted in prostate cancer patients whose initial PSA values were < or = 20 ng/ml: whereas positive slopes (i.e., increasing PSA levels during radiotherapy course) was seen in 7.1% of those with > 20 ng/ml preradiotherapy PSA values, such trends were seen in 52.7% of those with < or = 20 ng/ml preradiotherapy PSA values. CONCLUSIONS: (a) Incidental exposure of noncancerous prostate to ionizing irradiation appears to lead to an initial elevation followed by a decline in serum PSA. (b) Similar elevations in serum PSA levels are seen in over 50% of prostate cancer patients with < or = 20 ng/ml pretreatment PSA. (c) Acinal cell death and sudden release of PSA into the circulation is the most likely explanation for our observations, although other mechanism cannot be excluded. (d) Our observations have to be considered in modeling PSA kinetics induced by RT and in correlating such kinetics to long-term outcomes. (e) Our findings in the control group indicate that there appears to be no significant variation in serum PSA over many weeks under physiological conditions in normal healthy ambulatory men.

Can prostate-specific antigen levels predict bone scan evidence of metastases in newly diagnosed prostate cancer?

Staging in prostate cancer, as in any other cancer has significant ramifications in management. Currently, prostate-specific antigen (PSA) determination and the bone scan are two important procedures in the pretreatment staging workup of prostate cancer. PSA is a very useful serum tumor marker in the management of prostate cancer patients. We retrospectively evaluated 90 patients at the time of initial diagnosis of prostate cancer, all of whom had initial PSA levels measured, as well as bone scans obtained. In addition to the PSA level, we considered clinical stage and pathologic grade in the prediction of bone scan for metastases, at the time of initial diagnosis of prostate cancer. Negative predictive value for PSA values < 10 ng/ml (27 patients), clinical stage A (9 patients) and pathologic grade 1 (19 patients) was 100%. The number of patients with bone scan evidence of metastasis with < 10 ng/ml and > 10 ng/ml PSA levels were 0% (0/27 patients) and 27% (17/63 patients) (p = .0022 [Fisher's Exact test]; p = .003 [chi-square test]). In patients with higher stage (p = .688), grade (p = .039), or PSA levels (p = .0001), the incidence of bone metastases increased. However, none of these three parameters can predict reliably bone scan evidence of metastases (i.e., positive predictive value). The negative predictive values did not improve when a combination of the two or three of the above parameters were used.

Modified method for determining carcinoembryonic antigen in the presence of human anti-murine antibodies.

The increasing use of monoclonal antibodies (MAbs) for disease diagnosis and therapy has created a class of patients at risk for systematic error in clinical testing due to interference by human anti-murine antibodies (HAMA). HAMA interference is often difficult to detect and can cause either an increase or a decrease in apparent concentrations of antigen present. We undertook a clinical study to test a HAMA-resistant enzyme immunoassay (EIA) format for carcinoembryonic antigen (CEA) determination. Using the Food and Drug Administration-approved CEA-EIA Monoclonal One-Step Assay (Abbott) with the addition of an acid/heat extraction of patients' specimens, we found that the resulting CEA values accurately reflected the patients' status. We demonstrated that the acid/heat-extracted specimens yield linear dilution curves and show analytical recoveries of added CEA in the range of 76-123% in HAMA-positive specimens and 86-103% in HAMA-negative specimens. The correlation of CEA values in extracted vs unextracted specimens from 184 patients and control subjects was 0.9963. The CEA detection limit of the assay was 1.6 micrograms/L for the extracted samples.

Racial differences in prostate-specific antigen levels in patients with local-regional prostate cancer.

Prostate cancer is a significant health problem for blacks. The incidence and mortality rates are higher in blacks than in whites; blacks often present with a higher stage. Prostate-specific antigen (PSA) is a very useful serum marker in prostate cancer. We analyzed data from a cohort of 161 patients to determine whether there were any racial differences in PSA levels prior to treatment in local-regional prostate cancer. The immunoradiometric method was used to determine the PSA values. The mean PSA levels were significantly higher in blacks than in whites (P = 0.022), and the difference remained significant in multivariate analysis after adjusting for stage and grade (P = 0.020). However, when analyzed further, the difference was statistically significant in one hospital (P = 0.001) and not in another (P = 0.493). Thus, our results are not unequivocal, but our data do suggest that racial differences in PSA levels not accounted for by tumor stage or grade may exist. Assuming that the data truly reflect a racial difference, the cause(s) of this difference remains to be determined. It may exist because, within each clinical stage, blacks are presenting with a higher tumor cell burden, or it may be indicative of more aggressive biological behavior. The possibility that racial differences are due to socioeconomic factors was considered by estimating median income level from zip code of residence; although a correlation between socioeconomic status and PSA level was found, racial differences remained borderline significant (P = 0.055) after adjusting for income level (in addition to stage and grade).

Localized prostate cancer: use of serial prostate-specific antigen measurements during radiation therapy.

The serum half-life of prostate-specific antigen (PSA) after radical prostatectomy is about 3 days; to the authors' knowledge, the PSA half-life during radiation therapy (RT) has not been investigated with weekly serial measurements. To determine the rate of decline and the half-life of PSA, serial measurements were obtained during 6-8 weeks of external-beam RT for localized prostate cancer. PSA values were determined immediately before and approximately 24 hours after the first dose of RT; thereafter, weekly measurements were made. There was a downward trend in PSA levels in 19 patients, with a median half-life of 58.5 days; the mean decline was 1.6% per day. However, in four patients, PSA levels either rose and fell to pre-RT values or increased steadily. The effect of digital rectal examination (DRE) on PSA levels was also analyzed. When the dates of DRE and subsequent PSA levels were inspected, no increase in PSA levels subsequent to DRE was found, although three of the four patients in whom PSA levels did not decrease underwent multiple DREs. The authors found a statistically significant (P = .023) transient elevation in the mean PSA values after the first fraction of RT (2 Gy) was administered; the mechanism and importance of which are not known.