Validation of the Composite Autonomic Symptom Score 31 (COMPASS 31) for the assessment of symptoms of autonomic neuropathy in people with diabetes.

AIM: To validate the Composite Autonomic Symptom Score (COMPASS) 31, in its Italian version, for the diagnosis of diabetic cardiovascular autonomic neuropathy in a clinic-based, single-centre study. METHODS: A total of 73 participants with diabetes (age 55 ± 14 years) completed the COMPASS 31 questionnaire before undergoing cardiovascular autonomic neuropathy and diabetic polyneuropathy assessment according to cardiovascular reflex tests, neuropathic symptoms and signs, and vibration and thermal thresholds. RESULTS: The COMPASS 31 total weighted score differed between participants with and without cardiovascular autonomic neuropathy (29.9 ± 19.5 vs 16.1 ± 14.7; P = 0.003) and with and without diabetic polyneuropathy (28.9 ± 19.1 vs 12.7 ± 11.3; P < 0.0001). It was related to cardiovascular reflex tests score (rho = 0.38, P = 0.0013) as well as diabetic polyneuropathy symptoms (rho=0.61, P < 0.0001) and signs scores (rho = 0.49, P < 0.0001). Receiver-operating curve analysis showed a fair diagnostic accuracy of total score for cardiovascular autonomic neuropathy (area under the curve 0.748 ± 0.068, 95% CI 0.599-0.861) and diabetic polyneuropathy (area under the curve 0.742 ± 0.061, 95% CI 0.611-0.845). The best score thresholds were 16 for early cardiovascular autonomic neuropathy (sensitivity 75.0%, specificity 64.9%, positive predictive value 37.5% and negative predictive value 90.2%), and 17 for both confirmed cardiovascular autonomic neuropathy and diabetic polyneuropathy (sensitivity 70.0% and 65.5%, respectively; specificity 66.7% and 79.5%, respectively; positive predictive value 25.0% and 67.9%, respectively; and negative predictive value 93.0% and 77.8%, respectively). COMPASS 31 had a good internal consistency according to Cronbach's α coefficient of 0.73. CONCLUSIONS: COMPASS 31 can represent a valid, easy-to-use, quantitative assessment tool for autonomic symptoms in diabetic neuropathy, with a fair diagnostic accuracy for both cardiovascular autonomic neuropathy and diabetic polyneuropathy.

Matrix metalloproteinase (MMP)-9: A realiable marker for inflammation in early human trichinellosis.

Matrix Metalloproteinases (MMPs) are involved in many physiological and pathological processes. As regards parasitic infections, the role of these proteins has been particularly studied in malaria, neurocysticercosis and angiostrongyloidosis. Recently, we evaluated serum levels of MMP-9 and -2 (gelatinases) in mice experimentally infected with Trichinella spiralis or Trichinella pseudospiralis, which cause different degrees of myositis and we found their significant increase in the former and, at a lesser extent, in the latter, thus suggesting the possibility that these gelatinases, particularly MMP-9, represent a marker of inflammation. Our aim was to evaluate the levels of MMP-9 and 2 in trichinellosis patients, to assess their possible clinical significance. Serum samples from 31 Trichinella britovi-infected individuals (20 males and 11 females), living in Tuscany, Central Italy, were analysed for MMP-9 and MMP-2 serum levels. Patients acquired infection with Trichinella after consuming raw or undercooked meat of wild boar. Their median age was 49±0.33years (range from 7 to 91). Sera was collected before starting anti-inflammatory treatment, aliquoted and stored at -20°C until use. Sera from healthy subjects was considered as controls. The gelatinolytic activity of MMPs was analysed by gelatin zymography on 8% polyacrylamide-SDS gels containing 0.1% porcine gelatin, under non-reducing conditions. Clear bands corresponding to the digested areas were evaluated with an appropriate software. MMP-9 levels were additionally determined in 15 patients using a commercial ELISA kit for human MMP-9. The zymographic analysis of the gels showed the presence in serum samples of gelatinase bands at approximately 125-kDa, 92-kDa and 72-kDa, corresponding to the MMP-9/Neutrophil gelatinase-associated lipocalin (NGAL) complex and proenzyme forms of MMP-9 and MMP-2, respectively. A significant (p<0.01) increase in gelatinolytic activity in patients compared to the control group was observed for pro-MMP-9 in 25 out of 31. The mean increase in activity was 39.25%±16.67%. No significant differences were observed for pro-MMP-2 activity. The MMP-9 levels detected by ELISA showed significant correlation with zymographic data (r2=0.62, p<0.003) and were higher in more affected patients (suffering diarrhea, facial edemas and myalgia). In conclusion, MMP-9 might be considered as a marker of inflammation in T. britovi patients. On the contrary, MMP-2 did not result significantly different in patients, compared to controls.

Inhibition of Hedgehog signalling by NVP-LDE225 (Erismodegib) interferes with growth and invasion of human renal cell carcinoma cells.

BACKGROUND: Multiple lines of evidence support that the Hedgehog (Hh) signalling has a role in the maintenance and progression of different human cancers. Therefore, inhibition of the Hh pathway represents a valid anticancer therapeutic approach for renal cell carcinoma (RCC) patients. NVP-LDE225 is a Smoothened (Smo) antagonist that induces dose-related inhibition of Hh and Smo-dependent tumour growth. METHODS: We assayed the effects of NVP-LDE225 alone or in combination with everolimus or sunitinib on the growth and invasion of human RCC models both in vitro and in vivo. To this aim, we used a panel of human RCC models, comprising cells with acquired resistance to sunitinib - a multiple tyrosine kinase inhibitor approved as a first-line treatment for RCC. RESULTS: NVP-LDE225 cooperated with either everolimus or sunitinib to inhibit proliferation, migration, and invasion of RCC cells even in sunitinib-resistant (SuR) cells. Some major transducers involved in tumour cell motility, including paxillin, were also efficiently inhibited by the combination therapy, as demonstrated by western blot and confocal microscopy assays. Moreover, these combined treatments inhibited tumour growth and increased animal survival in nude mice xenografted with SuR RCC cells. Finally, lung micrometastasis formation was reduced when mice were treated with NVP-LDE225 plus everolimus or sunitinib, as evidenced by artificial metastatic assays. CONCLUSIONS: Hedgehog inhibition by NVP-LDE225 plus sunitinib or everolimus bolsters antitumour activity by interfering with tumour growth and metastatic spread, even in SuR cells. Thus, this new evidence puts forward a new promising therapeutic approach for RCC patients.

The dual PI3K/mTOR inhibitor PKI-587 enhances sensitivity to cetuximab in EGFR-resistant human head and neck cancer models.

BACKGROUND: Cetuximab is the only targeted agent approved for the treatment of head and neck squamous cell carcinomas (HNSCC), but low response rates and disease progression are frequently reported. As the phosphoinositide 3-kinase (PI3K) and the mammalian target of rapamycin (mTOR) pathways have an important role in the pathogenesis of HNSCC, we investigated their involvement in cetuximab resistance. METHODS: Different human squamous cancer cell lines sensitive or resistant to cetuximab were tested for the dual PI3K/mTOR inhibitor PF-05212384 (PKI-587), alone and in combination, both in vitro and in vivo. RESULTS: Treatment with PKI-587 enhances sensitivity to cetuximab in vitro, even in the condition of epidermal growth factor receptor (EGFR) resistance. The combination of the two drugs inhibits cells survival, impairs the activation of signalling pathways and induces apoptosis. Interestingly, although significant inhibition of proliferation is observed in all cell lines treated with PKI-587 in combination with cetuximab, activation of apoptosis is evident in sensitive but not in resistant cell lines, in which autophagy is pre-eminent. In nude mice xenografted with resistant Kyse30 cells, the combined treatment significantly reduces tumour growth and prolongs mice survival. CONCLUSIONS: Phosphoinositide 3-kinase/mammalian target of rapamycin inhibition has an important role in the rescue of cetuximab resistance. Different mechanisms of cell death are induced by combined treatment depending on basal anti-EGFR responsiveness.

Validation of DN4 as a screening tool for neuropathic pain in painful diabetic polyneuropathy.

AIMS: DN4 (Douleur Neuropathique en 4 Questions) is a screening tool for neuropathic pain consisting of interview questions (DN4-interview) and physical tests. It has not formally been validated in diabetes. We evaluated the validity and diagnostic accuracy of DN4 and DN4-interview in identifying neuropathic pain of painful diabetic polyneuropathy. METHODS: In 158 patients with diabetes, the presence of diabetic polyneuropathy and neuropathic pain was assessed using scoring system for symptoms and signs, quantitative sensory testing, nerve conduction studies, pain history, numerical rating scale, and Short-Form McGill Pain Questionnaire. Painful diabetic polyneuropathy was defined as the presence of diabetic polyneuropathy plus chronic neuropathic pain in the same area as neuropathic deficits. A blinded investigator performed DN4. RESULTS: The DN4 score was significantly related to all the neurological and electrophysiological measurements and to Short-Form McGill Pain Questionnaire (ρ = 0.58, P < 0.0001). DN4 and DN4-interview scores showed a high diagnostic accuracy for painful diabetic polyneuropathy with areas under the receiver operating characteristic curve of 0.94 and 0.93, respectively. At the cut-off of 4, DN4 displayed sensitivity of 80%, specificity of 92%, positive predictive value (PPV) of 82%, negative predictive value (NPV) of 91%, and likelihood ratio for a positive result (LR(+) ) of 9.6. At the cut-off of 3, DN4-interview showed sensitivity and specificity of 84%, PPV of 71%, NPV of 92%, and LR(+) of 5.3. CONCLUSIONS: This is the first validation study of DN4 for painful diabetic polyneuropathy, which supports its usefulness as both a screening tool for neuropathic pain in diabetes and a reliable component of the diagnostic work up for painful diabetic polyneuropathy.

Neuropad as a diagnostic tool for diabetic autonomic and sensorimotor neuropathy.

AIMS: The aim of the present study was to determine the diagnostic accuracy of the Neuropad sudomotor test for diabetic cardiovascular autonomic neuropathy (CAN) and diabetic polyneuropathy (DPN), the latter assessed using a multi-level diagnostic approach. METHODS: In 51 diabetic patients, CAN, symptoms and signs of DPN, vibration perception threshold (VPT), cold (CTT) and warm thermal perception thresholds (WTT) were measured. Neuropad response was determined as normal (complete colour change) or abnormal (absent or incomplete colour change). The time until the complete colour change (CCC time) was recorded. RESULTS: CCC time showed significant correlations with all the neurological parameters, the strongest of which were with Valsalva ratio (rho = -0.64, P < 0.0001), symptoms of DPN (rho = 0.66, P < 0.0001), postural hypotension (rho = 0.54, P = 0.0001) and CTT (rho = -0.54, P = 0.0001). CCC time showed moderate diagnostic accuracy for both CAN and DPN: the areas under the receiver operating characteristic (ROC) curves were 0.71 and 0.76, respectively. The diagnostic characteristics of three cut-off values of CCC time, identified by ROC analysis (i.e. 10, 15 and 18 min), were analysed. Compared with 10 min, the 15-min cut-off value provided better specificity (from 27% to 52% and from 31% to 62% for CAN and DPN, respectively) and a better likelihood ratio for negative result (from 0.67 to 0.34 and from 0.58 to 0.33) without lowering sensitivity (from 82% to 82% and from 85% to 80%). CONCLUSIONS: Neuropad is a reliable diagnostic tool for both CAN and DPN, albeit of only moderate accuracy. Extending the observation period to 15 min provides greater diagnostic usefulness.

Nighttime bracing with the Providence brace in adolescent girls with idiopathic scoliosis.

STUDY DESIGN: A prospective study was conducted of 102 consecutive female patients with adolescent idiopathic scoliosis. Those patients with Risser 0, 1, and 2 met the criteria for inclusion and were treated only with the Providence brace. OBJECTIVES: To report the authors' experience with a hypercorrective nighttime brace and to evaluate the results with respect to risk factors for progression. Second, the study compares results with expectations from the natural history as reported by others. SUMMARY OF BACKGROUND DATA: Compliance with full-time brace treatment for adolescent idiopathic scoliosis has been a problem. Since the introduction of the Milwaukee brace, alternatives such as low-profile braces, reduced wearing schedules, and nighttime only bracing have been tried. However, many factors influence the success or failure besides compliance. These include in-brace correction, brace design, and the orthotist's skills. This is the first report of the results of treatment with a new nighttime brace that is made with CAD/CAM technology that can achieve higher initial in-brace corrections than other reported methods. METHODS: Results were analyzed with respect to curve size, curve pattern, maturity, and level of the primary curve apex. Both compliant and noncompliant patients were included in the analysis. A univariate analysis was done on those factors thought to influence success with bracing using the Pearson chi2 test. RESULTS: The average initial in-brace correction with a supine radiograph was 96% for major curves and 98% for minor curves. Seventy-five patients (74%) did not progress >5 degrees and 27 patients (26%) progressed > or =6 degrees or went on to surgery. Twenty-nine percent of Risser 0 or 1 patients progressed and 17% of patients Risser 2 progressed. The risk of progression anticipated by natural history data, which included all curve patterns, was 68% for Risser 0 and 1 and 23% for Risser 2. Risser 3 and 4 patients were excluded from the study. Seventy-six percent of patients with curve apexes between T8 and L1 had successful outcomes using the Providence brace. This is compared with a 74% success rate in the prospective Scoliosis Research Society study of patients wearing a thoraco lumbar sacral orthosis for 16 hours per day with curve apexes between T8 and L1. With the Providence brace, 63% of thoracic curves and 65% of double curves were successful. Ninety-four percent of lumbar curves and 93% of thoracolumbar curves were successful. CONCLUSION: Excellent initial in-brace correction of adolescent idiopathic scoliosis was observed with this computer-designed and manufactured recumbent brace. Patients with high apex curves cephalad to T8 (n = 31) had a success rate of 61% compared with a success rate of 79% (n = 71) if the apex was at or below T9. Compared with previous natural history and the prospective study data, the Providence brace is effective in preventing progression of adolescent idiopathic scoliosis for curves <35 degrees. It was effective for larger curves with a low apex. The authors' experience with patients with curves >35 degrees (n = 8) is too small to validate its effectiveness for larger curves with a higher apex.

Neuropathological correlates of dysarthria in progressive supranuclear palsy.

BACKGROUND: The dysarthria of progressive supranuclear palsy consists of prominent hypokinetic and spastic components with less prominent ataxic components. OBJECTIVE: To correlate the types of dysarthria with neuropathological changes in patients with progressive supranuclear palsy. DESIGN AND METHODS: In 14 patients with progressive supranuclear palsy, we correlated the perceptual speech findings with the neuropathological findings. A dysarthria assessment was performed a mean +/- SD of 31 +/- 15 months (range, 10-53 months) before death. The deviant speech dimensions were rated on a scale of 0 (normal) to 3 (severe). The neuropathological examination consisted of semiquantitative analysis of neuronal loss and gliosis by investigators (A.A.F.S., and L.A.B.) blinded to the clinical findings. Correlation and linear regression analysis were used to correlate the severity of the hypokinetic, spastic, and ataxic components with the degree of neuronal loss and gliosis in predetermined anatomical sites. RESULTS: All patients had hypokinetic and spastic dysarthria, and 9 also had ataxic components. The severity of the hypokinetic components was significantly correlated with the degree of neuronal loss and gliosis in the substantia nigra pars compacta (r = 0.61, P =.02) and pars reticulata (r = 0.64, P =.01) but not in the subthalamic nucleus (r = 0.51, P =.07) or the striatum or globus pallidus (/r/<0.34, P>.20). The severity of the spastic and ataxic components was not significantly correlated with the neuropathological changes in the frontal cortex (r = 0.20, P =.50) and cerebellum (/r/<0.28, P>.33), respectively. CONCLUSION: The hypokinetic dysarthria of progressive supranuclear palsy may result from degenerative changes in the substantia nigra pars compacta and pars reticulata and not from changes in the striatum or globus pallidus.

The pathology of REM sleep behavior disorder with comorbid Lewy body dementia.

A patient with REM sleep behavior disorder who subsequently developed probable Lewy body dementia is now reported to have a definite pathologic diagnosis of Lewy body dementia. Examination of brain revealed Lewy bodies as well as marked neuronal loss in brainstem monoaminergic nuclei-particularly locus coeruleus and substantia nigra-that inhibit cholinergic neurons in the pedunculopontine nucleus mediating atonia during REM sleep.

A randomized trial comparing the introduction of ritonavir or indinavir in 1251 nucleoside-experienced patients with advanced HIV infection.

ISS-IP1, a multicenter, randomized, 48-week open trial, was designed to compare the introduction of ritonavir or indinavir in patients with previous nucleoside experience and CD4+ cell counts below 50/mm3. Concomitant antiretroviral treatment with nucleoside analogs was allowed. Primary efficacy measures were survival and time to a new AIDS-defining event or death, analyzed through the whole period of observation by the intention-to-treat approach. Primary toxicity measures were time to treatment discontinuation and adverse events, grade at least 3/serious, analyzed by an on-treatment approach. Evaluation-of efficacy also included CD4+ cell and RNA response. The trial enrolled 1251 patients in 5 months. At baseline, mean CD4+ cell count was about 20 cells/mm3 and mean HIV RNA copy number was 4.9 log10/ml in both groups. Overall, 402 patients in the ritonavir group and 250 patients in the indinavir group permanently discontinued the assigned treatment (relative risk, 1.96; 95% CI, 1.68-2.30; p = 0.0001), with most of this difference dependent on a higher number of discontinuation for adverse events in the ritonavir group. After a mean follow-up of 307 days (ritonavir, 304; indinavir, 309), 124 deaths (ritonavir, 61; indinavir, 63; relative risk, 0.96; 95% CI, 0.67-1.36; p = 0.80) and 330 new AIDS-defining events (ritonavir, 170; indinavir, 160; relative risk, 1.05; 95% CI, 0.85-1.31; p = 0.60) were observed. CD4+ cell counts increased in both groups in patients still receiving treatment, with about 100 cells gained by week 24 and 150 cells gained by week 48. Body weight also increased over time in both groups. Analysis of RNA response showed a decrease of 1.5 log10 or higher in both treatment groups. Overall, 400 patients in the ritonavir group and 338 patients in the indinavir group developed at least one grade 3/serious new adverse event during follow-up (relative risk, 1.48; 95% CI, 1.28-1.72; p = 0.0001). Favorable CD4+ cell and RNA responses at 24 and 48 weeks were observed in both groups of patients remaining on treatment. Indinavir showed slightly better effects in sustaining RNA, CD4+ cell, and body weight responses. Ritonavir and indinavir results were comparable in terms of clinical outcome (survival and AIDS-defining events).

Widespread alterations of alpha-synuclein in multiple system atrophy.

Glial cytoplasmic inclusions (GCI) are the hallmark of multiple system atrophy (MSA), a rare movement disorder frequently associated with autonomic dysfunction. In this study of 21 cases of MSA, GCI were consistently immunoreactive for alpha-synuclein and double-immunostained for ubiquitin and oligodendroglial markers, but not glial fibrillary acidic protein. No statistically significant difference was found in the density of GCI in various brain regions in the two forms of MSA, striatonigral degeneration (SND) and olivopontocerebellar atrophy (OPCA). Postmortem brain samples from 9 cases of MSA were fractionated according to solubility in buffer, Triton-X 100, sodium dodecyl sulfate (SDS), and formic acid, and alpha-synuclein immunoreactivity was measured in Western blots. Total alpha-synuclein immunoreactivity was increased in MSA compared to controls, with no statistically significant difference between SND and OPCA. Most of the increase was due to alpha-synuclein in SDS fractions. In controls this fraction had little or no immunoreactivity. In 7 cases and 4 controls correlations were investigated between quantitative neuropathology and biochemical properties of alpha-synuclein. Surprisingly, the amount of SDS-soluble alpha-synuclein correlated poorly with the number of GCI in adjacent sections. Furthermore, areas with few or no GCI unexpectedly had abundant SDS-soluble alpha-synuclein. These findings provide evidence that modifications of alpha-synuclein in MSA may be more widespread than obvious histopathology. Moreover, these alterations may constitute a biochemical signature for the synucleinopathies.

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.

Neuropathology of chromosome-17-linked dementia.

We describe the characteristic neuropathologic changes in chromosome-17-linked dementia. Identified cases to date demonstrate a uniform pathology consisting of neuronal loss, gliosis and vacuolization of frontal, anterior cingulate and temporal cortex and occipital association areas. Similar changes are present in substantia nigra, ventral striatum and amygdala. Hippocampus itself is spared, whereas the afferent perforant tract is consistently affected. Characteristic neuronal inclusions consisting of lattice-like neurofilaments are present in subcortical nuclei and glial cytoplasmic tau-positive inclusions are present throughout the white matter. These pathologic changes appear to be unique for chromosome-17-linked dementia.

Fluoxetine for migraine prophylaxis: a double-blind trial.

UNLABELLED: Selective serotonin reuptake inhibitors have recently been used in the treatment of migraine. OBJECTIVE: We studied the safety and efficacy of fluoxetine in the prevention of migraine. PATIENTS: Between February 1997 and December 1997, we examined 52 patients (33 women) at the Headache Diagnosis and Therapy Service of the Second University of Naples. Ages ranged from 18 to 65 years, and all patients suffered from migraine without aura according to IHS 1988 criteria. The sample was divided into two groups: group A included 32 patients (19 women; mean age, 36.8 years [SD 12.4]) who received fluoxetine at a dosage of 20 mg per day; group B included 20 patients (14 women; mean age, 38.8 years [SD 15.6]) who received placebo. METHODS: Our study was a single-center, randomized, double-blind, parallel study of fluoxetine for the prophylactic control of migraine and consisted of two phases: 30 days of pharmacological wash out and 6 months of therapy with monthly follow-up. Patients were randomly assigned to two groups: A, fluoxetine or B, placebo. At the first visit, patients provided a detailed history and underwent neurological evaluation and a Zung test for depression. No pathological values were revealed. In order to monitor symptomatology, all patients received a form for the calculation of the total pain index at monthly follow-up. RESULTS: A comparison of the total pain index between basal values (calculated during the period of wash out) and monthly follow-up (calculated monthly during the period of 6 months of the therapy) showed significant reduction (P < .05) beginning from the third month of treatment in the fluoxetine group and no significant reduction in the placebo group. CONCLUSION: Even if preliminary and to be confirmed, these data seem to support the use of fluoxetine in the treatment of migraine.

Clubfoot analysis with three-dimensional foot models.

The purpose of this study was to develop a method of defining, in mathematical terms, the interpositional relationships of the bones of the hindfoot complex in the idiopathic clubfoot and the neurogenic clubfoot. The neurogenic clubfoot and contralateral normal-appearing foot of a stillborn infant with myelomeningocele, and the normal foot of a 10-year-old were sectioned with a cryomicrotome. Magnetic resonance images (MRIs) of the clubfoot and the normal foot of a 3-month-old boy were obtained. Using a computer program, three-dimensional foot models were generated from the digitized cryomicrotome sections and from the MRIs. The central principal axes were determined for the talus and calcaneus. The long central principal axes of the talus and calcaneus were neutrally rotated with reference to the bimalleolar axis in the idiopathic clubfoot while in the neurogenic clubfoot the long central principal axis of the talus was medially rotated 52 degrees and that of the calcaneus 10 degrees. The talocalcaneal angles defined by the long central principal axes in the superior and medial views were 0 degree and 10 degrees, respectively, in the idiopathic clubfoot, and 42 degrees and 56 degrees, respectively, in the neurogenic clubfoot.

[Mycobacterium tuberculosis drug resistance in patients with HIV and pulmonary tuberculosis infections in Rome: 1987-1996]. / La farmaco-resistenza di Mycobacterium tuberculosis nei pazienti con infezione da HIV e tubercolosi polmonare in Roma: 1987-1996.

A retrospective chart review was performed on 118 HIV infected patients with pulmonary tuberculosis hospitalized between 1987 and 1996 in a tertiary care center for Infectious Diseases in Rome. The aims of this study were: a) to evaluate global prevalence of and risk factors for drug-resistant Mycobacterium tuberculosis and multidrug resistant tuberculosis; b) to assess trends in prevalence of drug-resistant tuberculosis over the 10-year study period. Prevalence of drug resistance of first Mycobacterium tuberculosis isolates was tested on Lowenstein-Jensen medium with the proportional method. Of the 118 patients studied, 83 had never been treated for tuberculosis and 35 had already been treated for at least 1 month. The overall prevalence of resistance to one or more drugs was 25% (17% in never treated patients vs 46% in already treated patients; p = 0.002). Five percent of isolates were resistant to both isoniazid and rifampin (1% in never treated patients vs 14% in already treated patients; p = 0.008). Resistance rates to individual drugs were: isoniazid 14%, rifampin 8%, ethambutol 0%, streptomycin 13%. During the study period no significant variations in prevalence of drug-resistant tuberculosis were found. In our area, empiric therapy should include 4 drugs: as well as isoniazid, rifampin and pyrazinamide, we recommend ethambutol. Surveillance of drug-resistant tuberculosis is needed. Directly observed therapy should be considered for HIV patients in order to prevent increases in drug resistance, relapses, and treatment failures.

Role of human immunodeficiency virus in primary pulmonary hypertension--case reports.

Previous cases of pulmonary hypertension (PH) in human immunodeficiency virus (HIV) infection have been reported in the literature. The role of HIV in PH is still debatable. The purpose of this report was to analyze whether HIV plays a direct or indirect role in PH pathogenesis. Between February and November 1997, 56 HIV-infected patients with cardiac symptoms and signs were studied by serial color Doppler echocardiography. In four patients (7.1%), PH not related to other well-known associated conditions, was disclosed. In spite of a low serum HIV RNA viral load and a high-efficacy antiretroviral therapy, including a protease inhibitor in two patients, PH developed and worsened. It could be hypothesized that in some patients with an individual immunogenetic predisposition, a high secretion of cytokines and endothelin-1 stimulated by an unidentified pathogen different from HIV could lead to PH. Antiretroviral therapy seems not to prevent or reduce right ventricle pressure gradient in PH.

Pulmonary cryptosporidiosis in patients with acquired immunodeficiency syndrome.

Several reports have showed Cryptosporidium species as a cause of intractable diarrhea and malabsorption in patients with acquired immunodeficiency syndrome (HIV). A case of chronic diarrhea in a drug addict woman associated with a symptomatic interstitial pulmonary infection due to Cryptosporidium parvum is described. This unusual C. parvum spread into the bronchial tree is underlined and a survey of the literature is made.

Frontotemporal dementia and parkinsonism linked to chromosome 17: a consensus conference. Conference Participants.

We held an international consensus conference on frontotemporal dementia, behavioral disturbances, and parkinsonism linked to chromosome 17 to determine whether these are homogeneous or heterogeneous disorders, to agree on terminology, and to develop strategies for further research. The group identified 13 kindreds with sufficient evidence for linkage, finding in common to all a critical 2 cM between markers D17S791 and D17S800. There was agreement that (1) despite previous descriptions that have emphasized one or another clinical or neuropathological feature, the kindreds share clinical and neuropathological features; (2) until more specific information about the genetic defects becomes available, this disorder is best termed frontotemporal dementia and parkinsonism linked to chromosome 17; and (3) further research will be enhanced by identifying the gene or genes responsible for this disorder, detecting additional cases within known families and, in new families, correlating mutations with phenotypes and more fully delineating the clinical, neuropsychological, and neuropathological characteristics of this disorder.