Positive and sustained effects of highly active antiretroviral therapy on HIV-1-associated neurocognitive impairment.

OBJECTIVES: To determine whether highly active antiretroviral therapy (HAART) is effective in HIV-associated neurocognitive impairment. DESIGN: An open label, prospective, observational study. METHODS: Since April 1996, 116 patients with advanced HIV infection, reverse transcriptase inhibitor (nRTI) experienced but protease inhibitor (PI) naive, were screened for the presence of neurocognitive impairment. Ninety patients with confounding neurological illness, opportunistic infections or drug abuse were excluded. The remaining 26 patients underwent comprehensive neuropsychological testing, and laboratory measures before, after 6 and after 15 months of treatment with one PI plus two nRTI. RESULTS: The prevalence of neurocognitive impairment decreased from 80.8% (baseline) to 50.0% (P<0.05) (sixth month) and to 21.7% (P<0.001) (15th month). Among the functions explored, the impairment of concentration and speed of mental processing decreased from 65.4 to 21.7% (P<0.01) and of memory impairment from 50 to 8.7% (P<0.01). Comparing baseline with the sixth and 15th month raw scores, a statistically significant improvement was seen in measures exploring concentration and speed of mental processing (P<0.05), mental flexibility (P<0.05), memory (P<0.05), fine motor functions (P<0.05) and visuospatial and constructional abilities (P<0.01). After 6 months of HAART patients with a normal neuropsychological examination had lower mean plasma viraemia (2.95 versus 3.97 log copies/ml, P<0.05) and greater mean log plasma HIV RNA changes from baseline (-1.84 versus -0.83 log copies/ml, P<0.05) than neuropsychologically impaired subjects. CONCLUSION: HAART produces a positive and sustained effect on neurocognitive impairment in HIV-infected patients. A reduction of plasma viral load was associated with the regression of neuropsychological test abnormalities.

Ischemic nephropathy in an elderly nephrologic and hypertensive population.

BACKGROUND: Atherosclerotic renovascular disease is a frequent cause of end-stage renal failure leading to dialysis in the elderly population. Its prevalence is known from autopsy or retrospective arteriographic investigations. This prospective study was conducted in 133 subjects with the inclusion criteria of hypertension and/or chronic renal failure starting after 50 years of age. Renal failure was unrelated to other known causes of renal disease. METHODS: The patients were subjected to echo-color doppler ultrasonography of renal arteries (104) and/or to renal scintigraphy (112). Thirteen of 27 patients with positivity using one or both noninvasive techniques were subjected to digital selective angiography. RESULTS: All the patients with positivity of echo-color doppler technique were true positives, with a consequent predictive value reaching 100%. Renal scintigraphy was of markedly lower predictive value. Based on the echo-color doppler investigation, percentage positivity for hemodynamically significant stenosis (> 50%) was 3.2 (16.3% had mild nonsignificant stenosis of renal arteries) in the 50- to 59-year-old group, 20% (plus 12.5% with nonsignificant stenosis) in the 60- to 69-year-old group and 25% (plus 17.8% nonsignificant stenosis) in the > 70-year age group. Patients with significant stenosis also had a significantly higher degree of renal insufficiency and received a higher number of hypotensive drugs (p < 0.013). The percentage of hypertensive patients was not different in the stenotic and nonstenotic groups. CONCLUSIONS: A large percentage of the elderly population is affected by renal vascular obstructive disease and is at risk of developing end-stage renal failure. Considering the wide number of cases with foreseeable renal arterial stenosis in the vast population meeting the selection criteria, it is possible to conclude that not all cases evolve to renal failure due to different rates of progression or to untimely nonrenal death.

Evaluation of the response to chemotherapy in patients affected with small cell lung cancer using discriminant analysis: a preliminary report.

This report represents an attempt to combine the serum levels of more tumor markers together to evaluate the response to chemotherapy in 26 patients affected with small cell lung cancer (SCLC), by means of discriminant analysis. A pilot prospective study was performed on 26 subjects affected with inoperable SCLC (18 extensive diseases, and 8 limited diseases) and treated with chemotherapy (etoposide plus cisplatin regimen). Serum levels of a panel of tumor markers: Carcinoembryonic antigen (CEA), Tissue Polypeptide Antigen (TPA), Neuron Specific Enolase (NSE) and CYFRA -21.1 were determined before starting chemotherapy and at the restaging time (after 3 months). To optimize the classification power of these markers, a discriminant analysis was done, which permitted generating two classification functions, based on Tissue Polypeptide Antigen and Neuron Specific Enolase levels able to correctly classify 25 out of 26 subjects (8 progressions and 18 non progressions). The results obtained, furtherly confirm that tumor markers are useful to evaluate the chemotherapy response and indicate a possible approach to obtain the maximum usefulness of the serum marker levels.

[Nuclear imaging in AIDS-related neurologic diseases]. / Imaging medico-nucleare nel neuro-AIDS.

A total of 356 patients with HIV-1 infection at different immunological and neurologic stages were included in this study. Patients with CNS opportunistic signs were excluded. All patients underwent SPET with HMPAO-99mTc; 166 patients were submitted to brain CT and 48 to MRI no later than 30 days after SPET examination. A control group of 12 intravenous drug users with no HIV infection was also examined. In the control group all SPET exams were negative; more positive SPET exams were observed with the progression of clinical and neurologic disease. No correlation was found between SPET positivity and immunological stage. In the asymptomatic stage 54% of SPET findings were positive. SPET was more sensitive than both CT and MRI in defining the abnormal changes of the earlier stages of this syndrome. Since opportunistic infections and neoplasms were excluded from this study and a control group was also considered, our results may indicate a major activity of HIV in the brain and suggest the need to monitor the earlier stages of this disease as well.

Somatostatin receptor imaging in small cell lung cancer using 111In-DTPA-octreotide: a preliminary study.

Small cell lung cancer is a common and aggressive disease. Combined multiagent chemotherapy and radiotherapy can improve short-term prognosis, but long-term prognosis remains dim. Somatostatin receptors have been identified on the cellular surface of subsets of this cancer and may be associated with less aggressive evolution. Moreover, medical therapy with somatostatin analogues holds promise for neoplastic growth control. Planar scintigraphy has been performed in 15 patients with histologically proven small cell lung cancer at 4 and 24 h after the intravenous (i.v.) injection of 185 MBq 111In-octreotide (Octreoscan, BYK-Gulden). No short-term adverse effects were recorded; tumour uptake of the radiopharmaceutical was observed in 13 patients at 4 h and in 12 patients at 24 h suggesting more extensive disease than apparent by computed tomography (CT). It is highly likely that the 24 h uptake reflects the presence of somatostatin receptors on the tumour. Previous chemotherapy does not seem to play a key role in tumour visualization. 111In-octreotide is a suitable radiopharmaceutical for in vivo evaluation of somatostatin receptor status of small cell lung cancer. Quantitative scintigraphic methods are needed to investigate nonspecific binding and receptor kinetics.

Effects of zidovudine in 30 patients with mild to end-stage AIDS dementia complex.

OBJECTIVE: Zidovudine (ZDV) is an inhibitor of HIV replication that may have a beneficial effect on patients with AIDS dementia complex (ADC). However, little is known about the association between long-term ZDV treatment and severity of ADC, ZDV dose or clinical and laboratory response to therapy. DESIGN: An open study on ZDV administration in 30 consecutive patients with ADC. SETTING: An infectious diseases hospital. PATIENTS: Thirty consecutive patients followed-up for 12 months. INTERVENTIONS: Three oral ZDV doses were used: 1000 mg (nine patients), 750 mg (eight patients) and 500 mg (13 patients) per day, depending on haematological status. MAIN OUTCOME MEASURES: Clinical and neurological examinations, neuropsychological evaluations, high-field brain magnetic resonance imaging (MRI) and 99mTc-HM-PAO single photon emission computerized tomography (SPECT). RESULTS: A favourable clinical response, defined as reversal to a less severe ADC stage (Price and Brew's criteria), was observed after 1, 3, 6, 9 and 12 months in 15, 22, 25, 19 and 14 patients, respectively. Neither severity of ADC at entry nor ZDV dose correlated with response to treatment. Seven patients died during the 12-month follow-up. The only factor associated with longer survival was ADC severity at entry (12-month survival, 0.94 and 0.53, in patients in stages 1 or 2 and in stages 3 or 4, respectively; P < 0.01). After 6-12 months of ZDV treatment six patients who initially responded to therapy showed a relapse in initial ADC stage, and two patients a less severe neurological deterioration. Neuropsychological evaluations showed significant improvement in the Wisconsin Card-Sorting test (P = 0.006 for categories, P = 0.029 for perseverative errors), which is particularly sensitive to cognitive and frontal-lobe type functions. Brain MRI revealed a reduction of the extent of white matter lesions in six out of 13 patients, who also showed clinical improvement. SPECT scanning revealed a reduction in the extent of uptake defects concomitant with clinical response in nine out of 14 patients. CONCLUSIONS: ZDV is effective in most patients with mild to end-stage ADC, although the benefit is sometimes only transient; several relapses and deaths occurred after the sixth month of treatment.

Methods for detecting early signs of AIDS dementia complex in asymptomatic HIV-1-infected subjects.

OBJECTIVES: To determine the optimal diagnostic procedures for identifying early signs of AIDS dementia complex (ADC) in asymptomatic HIV-1-infected individuals, in order to prevent further cognitive function impairment by early treatment. DESIGN: Study patients had been referred electively and consecutively to hospital; all had been referred for the first time and gave informed consent. Inclusion criteria were (1) lack of history and/or symptoms of psychosis and neurological disorders; (2) lack of active viral, protozoan or fungal pathology; (3) abstinence from heroin and/or cocaine for at least 6 months before baseline evaluation. SETTINGS: Subjects were seen at the L. Spallanzani Hospital for Infectious Diseases, Rome, Italy between March 1989 and March 1991. PARTICIPANTS: Eighty-two asymptomatic HIV-1-infected subjects: 41 drug users, 27 homosexuals and 14 heterosexuals. MAIN OUTCOME MEASURES: All subjects were evaluated using Wechsler-Bellevue I, Benton C form and Bender tests. Thirty-nine subjects underwent single-photon emission computed tomography (SPECT) and 12 magnetic resonance imaging (MRI). The immunological status of each subject was determined. RESULTS: On psychometric testing, 23 out of the 82 (28%) asymptomatic subjects had a mental decay percentage (MD%) > or = 20%. Cerebral perfusion abnormalities were detected in 31 out of 39 (79.48%) subjects who underwent SPECT; MRI abnormalities were observed in seven out of 12 (58%) subjects. Twelve out of 23 subjects with MD% > or = 20, 15 out of 29 subjects with SPECT abnormalities and four out of seven patients with MRI abnormalities had total CD4+ lymphocyte counts > or = 500 x 10(6)/l. CONCLUSIONS: The high incidence of abnormal SPECT and of MD% > or = 20 in asymptomatic HIV-1-infected patients, and the lack of correlation between immunological status and degree of mental decay, SPECT and MRI abnormalities raise many questions about subclinical HIV-1 neurological disease.

Cerebral blood flow in AIDS-related neurotoxoplasmosis: a preliminary 99mTc-HMPAO SPECT study.

Cerebral blood flow (CBF) was evaluated by gamma camera 99mTc-HMPAO SPECT in 11 patients with AIDS-related neurotoxoplasmosis and correlated with neurological findings and the results of CT and MRI. Evident CBF abnormalities were observed in all patients with involvement of at least two cerebral lobes. In 10 patients the abnormalities were bilateral and in 8 patients basal ganglia were involved; no specific hypoperfusion pattern was however evident. Focal lesions were found in 7 patients by CT (sensitivity: 63.6%) and in 10 patients by MRI (sensitivity: 90.9%). It may be concluded that neurotoxoplasmosis in AIDS patients is associated with a high prevalence of focal cortical and subcortical hypoperfusion but that the scintigraphic findings are not specific; that HMPAO SPECT may show focal hypoperfusion in patients with normal CT studies and/or non-focal MRI abnormalities; that the hypoperfusion may be more extensive than the corresponding MRI lesion(s) and that it may be present even in areas with normal MRI signals; and that more experience and longitudinal studies are needed to assess the possible impact of HMPAO SPECT on follow-up and therapy monitoring.

Cortical cerebral blood flow in HIV-1-related dementia complex.

Dementia complex is a syndrome that affects a high percentage of AIDS patients. Neuroradiological findings may be non-specific and the diagnosis can be difficult in its earlier stages. Preliminary radionuclide studies have recently reported derangements of regional cerebral blood flow (CBF) which may be present before overt anatomical injury. This study reports on cortical and cerebellar CBF changes in 26 patients studied with 99Tcm-HM-PAO and single photon emission computed tomography (SPECT). Extensive cortical CBF derangements were observed in all patients and an evident cerebellar hypoperfusion was also present in three. The prevalence of hypoperfusion was highest in the frontal and parietal lobes. The extension of the hypoperfusion showed a highly significant correlation with the severity of the dementia complex (P less than 0.01 by chi 2 test). The SPECT also showed hypoperfused areas in three patients with normal CT scans and in two patients with normal MRI scans. These results confirm previous preliminary reports on the high prevalence of cortical hypoperfusion in dementia complex and suggest the use of this radionuclide technique to assist in the early diagnosis and follow-up of AIDS patients, especially when CT and MRI are still normal.

The influence of age on the pulmonary clearance of 99Tcm-DTPA radioaerosol.

Age-dependent changes of 99Tcm-DTPA radioaerosol transpulmonary clearance have been investigated in 49 healthy volunteers with an age range of 21-63 years. The clearance was uniformly increased in all smokers irrespective of age, but it showed a highly significant (p less than 0.001) decrease in non-smoking patients over 50 years. Several age-related changes in the ageing lung can contribute to this decreased clearance, but the reduced alveolar-capillary surface area available for the transport is probably the key factor. The practical implication of the results is the need to use age-related normal ranges when interpreting 99Tcm-DTPA radioaerosol clearance studies.

Plasma carcinoembryonic antigen and tissue polypeptide antigen levels in lung cancer: correlation with cell types and stage.

This investigation was carried out to evaluate the plasma CEA and TPA levels in normal subjects and in 140 patients with lung cancer: 116 patients with nonsmall cell lung cancer (NSCLC) and 24 patients with small cell carcinoma (SCLC). The CEA and TPA levels were determined simultaneously by radioimmunoassay. The cutoff limit of CEA was found to be 17 U/SORIN, and the cutoff of TPA was 99 U/L. TPA has shown a sensitivity almost twice that of CEA. The relationship between the mean values of CEA and TPA and the stages of NSCLC was statistically significant (P less than 0.01), whereas only the mean values of TPA significantly (P less than 0.05) correlated with extensive and limited disease in SCLC. The determinations of combined CEA and TPA levels (CEA X TPA) (P less than 0.001) correlated significantly with the stage of disease in patients with NSCLC; conversely, the use of CEA X TPA did not correlate with the stage of SCLC.