Neuropsychological function and cerebral metabolites in HIV-infected youth.

The effects of HIV on brain metabolites and cognitive function are not well understood. Sixteen HIV+youths (15 vertical, 1 transfusion transmissions) receiving combination antiretroviral therapy and 14 age-matched HIV- youths (13-25 years of age) were evaluated with brain two-dimensional (2D) magnetic resonance spectroscopy (MRS) at 3 Tesla (T) and a neuropsychological battery that assessed three cognitive domains (attention/processing speed, psychomotor ability, and executive function). The relationship between brain metabolite ratios and cognitive performance was explored. Compared to HIV- controls, HIV+ subjects had higher sycllo-inositol (Scy)/total creatine (tCr) (+32%, p = 0.016) and higher Scy/total choline (tCho) (+31%, p = 0.018) on 2D-MRS in the right frontal lobe. HIV+ subjects also had higher glutamate (Glu)/tCr (+13%, p = 0.022) and higher Glu/tCho (+15%, p = 0.048) than controls. HIV+ subjects demonstrated poorer attention/processing speed (p = 0.011, d = 1.03) but similar psychomotor and executive function compared to HIV- controls. The attention/processing score also correlated negatively with the ratio of N-acetylaspartate (NAA) to tCr on 2D-MRS (r = -0.75, p = 0.0019) in the HIV- controls, but not in the HIV+ subjects (Fisher's r-z transformation, p < 0.05). Our results suggest that attention/processing speed is impacted by early HIV infection and is associated with right hemisphere NAA/tCr. Scy and Glu ratios are also potential markers of brain health in chronic, lifelong HIV infection in perinatally infected youths receiving antiretroviral therapy.

Reoperative parathyroidectomy in the era of localization technology.

BACKGROUND: Recurrent and/or persistent hyperparathyroidism (HPT) is an uncommon disease. Relatively few cases are seen by any one center or surgeon. Most of the prior reviews of this problem were done in the era prior to potentially accurate magnetic resonsance imaging (MRI) and sestimibi scan localization and do not reflect current preoperative localization technology. METHODS: All cases of recurrent or persistent parathyroidectomy seen in our institution between 1992 and 1996 were reviewed retrospectively to assess the predictive value of preoperative MRI, selective venous sampling, sestimibi scanning, ultrasound examination, and computerized tomography (CT) scanning. The preoperative localization studies were compared with the findings at operation, the pathology report, and the patient's long-term calcium status. RESULTS: Twenty-eight patients were operated upon at our institution for recurrent or persistent HPT during this time interval. The final pathology turned out to be: adenoma, 24; hyperplasia, 2; carcinoma, 2. The site at which the reoperative pathology was found was in the neck in 22 patients and intrathoracic requiring sternotomy in 6. The long-term outcome, i.e., serum calcium level at > 6 months postoperatively, was normocalcemia in 22 of 28 (85%), persistent hypocalcemia in 2 of 28, and persistent hypercalcemia in 2 of 28. Some combination of MRI, sestimibi, selective venous sampling, ultrasound, and CT scan was performed on all patients preoperatively. Preoperative MRI scans were performed on 26 of 28 patients. They correctly localized the side and site of the pathology in only 12, yielding a sensitivity of 66%. There were, however, no false positives; therefore, the positive predictive value of this test was 100%. Selective venous sampling was carried out on 26 of 28 patients and correctly localized in only 8 (sensitivity, 50%). Again, there were no false positives, yielding a positive predictive value of 100%. Sestimibi scanning was performed in 16 of 28, localizing in 8 (sensitivity, 50%). The positive predictive value of this test was 80%. Ultrasound was performed in 26 of 28 patients and localized in only 3, yielding a sensitivity of 17%, with a positive predictive value of 75%. Computerized tomographic scan was performed preoperatively only when all other investigations turned out to have been nonlocalizing and was therefore done in only four patients, one of whom had a positive CT scan showing an intrathoracic, intrapericardial adenoma. CONCLUSIONS: These data demonstrate that despite the availability of what are putatively accurate preoperative localizing tests for previously unoperated cases, no one localizing test is particularly sensitive in reoperative parathyroid surgery. Magnetic resonance imaging and selective venous sampling, however, are complementary and when positive do accurately predict the site of the persistent/recurrent parathyroid pathology. Use of these preoperative localizing studies resulted in a successful outcome, i.e., normocalcemia or hypocalcemia in 93% of patients operated on.

Detection of pituitary microadenomas: comparison of dynamic keyhole fast spin-echo, unenhanced, and conventional contrast-enhanced MR imaging.

OBJECTIVE: Pituitary microadenomas may not be detected on conventional MR images. We supplemented conventional unenhanced and contrast-enhanced MR imaging with a dynamic keyhole fast spin-echo (kFSE) method in order to compare how frequently a microadenoma could be detected with the three different methods. SUBJECTS AND METHODS: Eighteen consecutive patients with clinical and laboratory evidence of pituitary microadenomas had unenhanced, dynamic kFSE, and conventional contrast-enhanced MR imaging of the pituitary gland. A control group of 13 subjects without pituitary disease also had dynamic kFSE MR imaging. Hard copies of all the studies were obtained in an identical fashion, and then the MR images of the patients and control subjects were randomly mixed. The studies were reviewed by a neuroradiologist who had no knowledge of the clinical status of the subjects. The presence or absence of any pituitary focal hypointensity consistent with the appearance of a microadenoma was noted. RESULTS: A pituitary lesion consistent in appearance with a microadenoma was detected on dynamic kFSE images in 13 of the 18 patients, on unenhanced images in nine patients, and on conventional contrast-enhanced images in 10 patients. In four patients, a microadenoma was detected on dynamic kFSE images only. Dynamic kFSE images showed a lesion in four of the 13 control subjects. CONCLUSION: Dynamic kFSE MR imaging is a useful supplemental sequence in patients undergoing MR imaging because of pituitary endocrinopathy. It may show lesions that would otherwise escape detection.

Immunoglobulin G subclasses in human colostrum, milk and saliva.

Previous studies have suggested local production of IgG4 in human colostrum and mature milk. We extended these observations to examine all IgG subclasses in mammary secretions and in saliva, a mucosal secretion. In human colostrum and milk, the geometric mean percentages of IgG contributed by IgG2 were 44% and 43%, respectively, and by IgG4, 6% in both. These percentages are significantly increased compared to the contributions in matched plasma, 29% for IgG2 and 2% for IgG4. The contribution of IgG1 (47%) and IgG3 (less than 4%) were decreased compared to plasma which contained 64% IgG1 and 6% IgG3. Similarly, in salivary secretions the percentages of IgG contributed by IgG2 and IgG4 were increased compared to serum while the percentage of IgG1 was decreased. IgG3 was not measurable in any saliva specimen by the technique used. These data demonstrate that IgG subclass distribution in two separate mucosal secretions is uniquely different from that in matching plasma or serum.

IgG4 in human colostrum and human milk: continued local production or selective transport from serum.

Colostrum, mature milk, and paired plasma samples were obtained from 10 postpartum women who had not been previously studied. The geometric mean concentration of IgG4 in colostrum (3.3 micrograms/ml) was similar to the mean concentration in mature milk (3.0 micrograms/ml). The arithmetic mean for the percent of IgG = IgG4 was 10.3 +/- 3.3% for colostrum, 10.3 +/- 3.1% for mature milk, 2.6 +/- 0.3% for early plasma, and 1.7 +/- 0.3% for later plasma. Local mammary production of immunoglobulin was determined by subtracting the estimated serum contribution from the measured concentration in colostrum or milk. Evidence for local mammary production of IgG4 was found in 5 of 10 colostrum samples and 8 of 10 mature milk samples. These observations indicate that the previously observed selective enrichment of IgG4 in colostrum is also true for mature milk. These are the first studies suggesting continued local production of any immunoglobulin other than IgA in mature human breast milk.

T cell subsets in human colostrum.

Lymphocytes from 10 paired colostrum and peripheral blood specimens were examined to determine if the colostral T cell population differs from the peripheral blood T cell population in subset distribution. The percentages of lymphocytes staining with OKT3, OKT4, and OKT8 murine monoclonal antibody were determined. Lymphocytes from colostrum were 74.7 +/- 2.5% OKT3+, 50.6 +/- 2.3% OKT4+, 24.0 +/- 1.7% OKT8+, whereas peripheral blood lymphocytes were 78.7 +/- 1.9% OKT3+, 48.4 +/- 1.4% OKT4+, and 29.8 +/- 1.6% OKT8+. The percentage of colostrum lymphocytes positive for OKT3 was significantly although not strikingly lower than the OKT3 percentage for blood lymphocytes (p less than 0.05). This difference was due to the lower percentage of OKT8 positive lymphocytes in colostrum compared with blood (p less than 0.01). Although the T cell subset distribution of colostrum generally appears to be similar to that in the peripheral blood, there were small differences in OKT3 and OKT8 percentages that were statistically significant suggesting the possibility of some selectivity of the colostral T cell population.

IgD in human colostrum.

Simultaneous colostrum (C) and plasma samples (P) from 14 women, 1 to 5 days postpartum, were examined. Total IgD and specific IgD antibodies to beta-lactoglobulin, bovine serum albumin, Bermuda grass, and alpha-gliadin were measured by solid phase radioimmunoassay. The geometric mean concentrations of IgD were 35.8 (range 2.2-410) micrograms/dl for colostrum and 591.3 (range 72-4100) micrograms/dl for plasma. Six subjects had a specific IgD antibody C/P ratio more than 10-fold greater than the total IgD C/P ratio, suggesting enhancement of antibody to a specific antigen in the mammary gland. All six had C/P ratios suggestive of local enhancement of IgD antibody to Bermuda grass, and two met this criterion for enhancement of IgD antibodies to beta-lactoglobulin, bovine serum albumin, or alpha-gliadin. Specimens for these studies were obtained during the peak grass pollen season. Seventeen additional subjects were studied to compare total IgD in colostrum and plasma with total IgG and serum albumin. The mean C/P ratio for IgD (0.055 +/- 0.015) exceeded the C/P ratio for total IgG (0.015 +/- 0.003) or total albumin (0.020 +/- 0.002). For 14 of 17 subjects the colostrum/plasma ratio for IgD exceeded the C/P ratio for albumin or IgG. Data were transformed logarithmically and correlation coefficients calculated. For albumin versus IgG in colostrum, there was a strong correlation, r = 0.865, p = 0.001. This was different from albumin versus IgD, r = 0.489, p = 0.046 and from IgD versus IgG, r = 0.556, p = 0.020. These analyses support a different mechanism of entry of IgD into milk compared to IgG or albumin.(ABSTRACT TRUNCATED AT 250 WORDS)

Local production of IgG4 in human colostrum.

Total IgG4 levels were determined in 27 colostrum and 27 plasma paired samples by using RIA techniques, and total IgG was determined on the same pairs by using radial immunodiffusion. In colostrum, the mean IgG4 level was 4.6 micrograms/ml (0.6 to 19.0), and in the plasma the mean IgG4 level was 170.5 micrograms/ml (30 to 920). IgG averaged 42.3 micrograms/ml (12 to 240) in colostrum and 7980.9 micrograms/ml (3250 to 16,000) in plasma. Of colostral IgG, 15.3% was IgG4, whereas only 3.5% of plasma IgG was IgG4. Specific IgG4 antibodies to beta-lactoglobulin, bovine serum albumin, bermuda grass, and alpha-gliadin were also assayed. In six patients, strong evidence was found for local mammary production of IgG4-specific antibodies.

IgE and IgD in human colostrum and plasma.

Using radioimmunoassay techniques, we measured IgE and IgD levels in paired colostrum and plasma samples obtained within 4 days postpartum. In colostrum, IgE was detected in concentrations of 0.5-6 IU/ml in 16 out of 39 samples (41%) and less than 0.5 IU/ml in the remainder, whereas IgD was detected in all samples in concentrations of 2-2000 micrograms/dl. Only a moderate correlation was found between colostral and plasma levels of both IgE (r = +0.60) and IgD (r = +0.74). The correlation coefficient between IgE and IgD in plasma was 0.23, whereas in colostrum it was only 0.05. The colostrum:plasma ratio of IgE varied strikingly from that of IgD; the ratio of IgD was 0.1-22.2 times that of IgE. The findings argue against passive transfer of IgE and IgD from the circulation of milk and suggest possible local mammary production of either or both of these two immunoglobulins.