Induction of prolonged survival of CD4+ T lymphocytes by intermittent IL-2 therapy in HIV-infected patients

HIV infection leads to decreases in the number of CD4 T lymphocytes and an increased risk for opportunistic infections and neoplasms. The administration of intermittent cycles of IL-2 to HIV-infected patients can lead to profound increases (often greater than 100%) in CD4 cell number and percentage. Using in vivo labeling with 2H-glucose and BrdU, we have been able to demonstrate that, although therapy with IL-2 leads to high levels of proliferation of CD4 as well as CD8 lymphocytes, it is a remarkable preferential increase in survival of CD4 cells (with half-lives that can exceed 3 years) that is critical to the sustained expansion of these cells. This increased survival was time-dependent: the median half-life, as determined by semiempirical modeling, of labeled CD4 cells in 6 patients increased from 1.7 weeks following an early IL-2 cycle to 28.7 weeks following a later cycle, while CD8 cells showed no change in the median half-life. Examination of lymphocyte subsets demonstrated that phenotypically naive (CD27+CD45RO-) as well as central memory (CD27+CD45RO+) CD4 cells were preferentially expanded, suggesting that IL-2 can help maintain cells important for host defense against new antigens as well as for long-term memory to opportunistic pathogens.     

Depression in schizophrenia: recognition and management in the USA

The recognition of depression as a distinct syndrome within schizophrenia is a relatively recent development. The International Survey of Depression in Schizophrenia was designed to evaluate current clinical practice and prescribing trends in the management of the depressive component of schizophrenia. A 48-item questionnaire, comprising fixed-response questions and questions stimulated by case scenarios, was distributed to 37513 psychiatrists in the USA. A total of 43484 psychiatrists in Canada, Australia and 21 European countries also received the questionnaire. A total of 1128 US psychiatrists responded. Analysis of the data revealed that US psychiatrists identify symptoms of depression in approximately one-third of patients with schizophrenia, and largely appreciate the magnitude of the resultant burden on patients and their families. Responses to questions regarding treatment approaches and case scenarios demonstrated that the level of adjunctive prescribing of antidepressants in the USA is often higher than in other regions. Levels of awareness of depression in patients with schizophrenia and recognition of the need for effective management appear to be high among US psychiatrists. However, more than a quarter of these specialists rarely or never prescribe adjunctive antidepressant medications. Disparities in treatment approaches varying from the existing scientific evidence base underscore the need for further investigation into ways of optimizing the management of this serious coexisting condition.     

Direct identification of ventrointermediate nucleus of the thalamus on magnetic resonance and computed tomography images

OBJECTIVE

The ventro-intermediate (Vim) nucleus of the thalamus is a commonly used target for the treatment of tremor. The thalamic fasciculus contains myelinated fibers, believed to play a role in the generation of tremor, that converge into a dense bundle at the inferior aspect of the Vim nucleus, making it visible on magnetic resonance (MR) and computed tomography (CT) images. This structure, therefore, can be visualized directly and targeted for thalamotomy.

METHODS

Thalamotomies were performed on nine patients (who have a follow-up of 13–23 months) with parkinsonian and essential tremors using MR and CT images. The tremor target was hypointense on MR images obtained in inversion recovery sequence and hypointense on CT images. It was therefore visualized, directly targeted, and probed. Stimulation studies were done to physiologically confirm accuracy of the probe placement and then a radiofrequency lesion was made.

RESULTS

Stimulation of the target identified as the Vim nucleus on MR and CT images produced responses similar to those expected from the Vim nucleus. After this site was lesioned tremor disappeared in all nine patients.

CONCLUSION

The Vim nucleus of the thalamus is visible on MR and CT images. Destruction of this target abolishes parkinsonian and essential tremors.     

Carbon residence time dominates uncertainty in terrestrial vegetation responses to future climate and atmospheric CO2

Future climate change and increasing atmospheric CO₂ are expected to cause major changes in vegetation structure and function over large fractions of the global land surface. Seven global vegetation models are used to analyze possible responses to future climate simulated by a range of general circulation models run under all four representative concentration pathway scenarios of changing concentrations of greenhouse gases. All 110 simulations predict an increase in global vegetation carbon to 2100, but with substantial variation between vegetation models. For example, at 4 °C of global land surface warming (510–758 ppm of CO₂), vegetation carbon increases by 52–477 Pg C (224 Pg C mean), mainly due to CO₂ fertilization of photosynthesis. Simulations agree on large regional increases across much of the boreal forest, western Amazonia, central Africa, western China, and southeast Asia, with reductions across southwestern North America, central South America, southern Mediterranean areas, southwestern Africa, and southwestern Australia. Four vegetation models display discontinuities across 4 °C of warming, indicating global thresholds in the balance of positive and negative influences on productivity and biomass. In contrast to previous global vegetation model studies, we emphasize the importance of uncertainties in projected changes in carbon residence times. We find, when all seven models are considered for one representative concentration pathway × general circulation model combination, such uncertainties explain 30% more variation in modeled vegetation carbon change than responses of net primary productivity alone, increasing to 151% for non-HYBRID4 models. A change in research priorities away from production and toward structural dynamics and demographic processes is recommended.     

Differential Effects of the M1–M5 Muscarinic Acetylcholine Receptor Subtypes on Intracellular Calcium and on the Incorporation of Choline Into Membrane Lipids in Genetically Modified Chinese Hamster Ovary Cell Lines

We compared responses of Chinese hamster ovary (CHO) cell lines stably transfected with human genes for the M₁–M₅ muscarinic receptor subtypes to several stimuli. While ATP brought about similar increases in the concentration of intracellular Ca²⁺ ions ([Ca²⁺]_i) in the cell lines expressing all individual receptor subtypes, carbachol acted with much higher potency and efficacy on the cells expressing the M₁, M₃, and M₅ receptor subtypes than on those expressing the M₂ and M₄ subtypes. The maximum [Ca²⁺]_i responses to ATP corresponded to 41–75% of the maximum responses to carbachol in the cells expressing the M₁, M₃, and M₅ receptor subtypes. The responses to ATP were strongly suppressed (> 75% decrease) by a preliminary administration of a maximally active concentration of carbachol in these three cell lines, whereas the responses to carbachol were less sensitive to the preliminary administration of a maximally active concentration of ATP (< 25% decrease). It appears likely that carbachol and ATP release Ca²⁺ ions from identical intracellular stores. Tetradecanoylphorbol acetate (TPA) strongly inhibited the responses of [Ca²⁺]_i to both carbachol and ATP and enhanced the incorporation of [¹⁴C]choline into lipids in all five CHO cell lines investigated. On the other hand, the incorporation of [¹⁴C]choline into lipids was diminished by carbachol in the cell line expressing the M₃ receptor subtype and unchanged in the other cell lines. This effect of carbachol was not dependent on the presence of extracellular Ca²⁺ ions and was not affected by TPA, which diminished the response of [Ca²⁺]_i to muscarinic stimulation. It is suggested that it was due to muscarinic receptor-mediated activation of phospholipase D. Copyright © 1997 Elsevier Science Inc.     

Current treatment for human immunodeficiency virus infection

Treatment of human immunodeficiency virus (HIV) infection can prolong survival and enhance the quality of life in affected patients, although neither immune reconstitution nor cure can be achieved. Zidovudine is now the only licensed treatment. It is effective but sometimes toxic. Zidovudine decreases the incidence of opportunistic infections but does not prevent them, and concurrent prophylaxis against Pneumocystis carinii pneumonia should be given to those patients at greatest risk of this infection. Most patients should have serial CD4+ T-cell determinations to assess their degree of immunodeficiency. Many investigational anti-HIV agents are being studied, and future treatments are likely to use multiple agents in combination or in sequence over many years.     

Hyperfunctioning and nonhyperfunctioning benign adrenal cortical lesions: characterization and comparison with MR imaging

The authors evaluated the potential of magnetic resonance (MR) imaging at 0.35 T to permit differentiation of nine hyperfunctioning adrenal cortical lesions from 21 nonhyperfunctioning adrenal cortical adenomas. Both qualitative data (visual assessment) and quantitative data (signal intensity ratios, T1, and T2) were used for tissue characterization. With a 2,000/56-100 sequence (repetition time msec/echo time msec), the majority of lesions were visually isointense to liver. Of 34 quantitative measures, only lesion-liver and lesion-kidney intensity ratios at 2,000/150 showed statistically significant differences among nonhyperfunctioning adenomas, aldosterone-producing lesions, and corticosteroid-producing lesions; however, the authors question the significance of these differences because of the abundant noise associated with the 2,000/150 sequence. The results suggest that nonhyperfunctioning adrenal cortical adenomas cannot be distinguished from benign hyperfunctioning cortical lesions with use of MR imaging at 0.35 T.     

Adrenal masses in oncologic patients: functional and morphologic evaluation

The role of adrenocortical scintigraphy in the evaluation of unilateral adrenal masses detected with computed tomography (CT) in 28 oncologic patients with normal adrenal function was studied prospectively with the use of NP-59 (iodine-131-6-iodomethyl-19-norcholesterol). The diagnosis was proved by means of percutaneous fine-needle aspiration cytologic examination in 20 patients, surgical biopsy in one, and clinical and CT follow-up in seven. In 14 of the 28 patients, there was increased uptake of the NP-59 on the side of the adrenal mass detected at CT (concordant uptake). Thirteen of the 14 masses with concordant uptake were greater than 2 cm in diameter, and one was 1.5 cm; all were found to be adenomas. In 11 of 28 patients there was decreased uptake on the side of the mass detected at CT (discordant uptake). None of these 11 masses were adenomas; nine were metastases and two were adrenal cysts. Uptake was indeterminate (symmetric) in three patients, two of whom had adrenal adenomas and one an adrenal metastasis; each mass with indeterminate uptake was less than 2 cm in diameter.     

Ocular complications in renal transplant patients

One hundred and seventy-six patients who received a renal transplant between 1982 and 1988 were examined for ocular complications of steroid therapy. Posterior subcapsular cataracts (PSC) were present in 60 patients (34.1%). Patients were classified into three groups (HS, LS, NoS) depending on their maintenance immunosuppression therapy. The HS group received high doses of steroids after renal transplantation. LS had low steroid doses, and NoS had no steroids. The incidence of PSC was 21 of 38 in HS (55.3%), 33 of 117 in LS (28.2%), and 1 of 16 in NoS (6.2%). The difference between HS and LS was statistically significant (x²= 8.1, P < 0.01). Grading the severity of PSC (PSC 0, PSC +, PSC > ++) showed a significant correlation between the degree of PSC and the steroid therapy. In the HS group, five patients had PSC +, and 16 had PSC > ++ (76%), compared to 19 patients with PSC +,14 patients with PSC > ++ (42%) in the LS group (x²= 4.6; P < 0.05). There was no correlation between the incidence of PSC and use of steroids for more than three months before dialysis. Comparison with the results of our earlier series (1973 -1981)¹ using high doses of steroids showed a similar incidence of PSC with HS (40.7% Series 1; 55.3% Series 2) but a lower incidence with LS and NoS.