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Biomedical subjects

S Miller

Publications and source records attributed to S Miller.

At least 181 records · Page 10Linked to original sources
PubMed1998

Human immunodeficiency virus sexual risk reduction in homeless men with mental illness.

BACKGROUND: The spread of human immunodeficiency virus infection to impaired groups has intensified the challenge for its prevention; control of the epidemic now requires behavioral change among persons with limited ability to sustain attention and learn. In this randomized clinical trial, we tested an intervention to reduce sexual risk behaviors among homeless men with severe mental illness. METHODS: Men were recruited from a psychiatric program in a homeless shelter. Of 116 eligible men, 97 (83.6%) participated. Most were African American and had a chronic psychotic disorder and a comorbid substance use disorder. Participants were assigned to a 15-session experimental group intervention or to a 2-session control intervention and observed for 18 months. The 59 participants sexually active before the trial were the main target of the intervention. Sexual risk behavior was the primary outcome. RESULTS: Among the 59 sexually active men, follow-up data were obtained on 59 (100%) for the initial 6-month follow-up and on 56 (95%) for the remainder of the 18-month follow-up. The mean score on a sexual risk index for the experimental group was 3 times lower than for the control group (1.0 vs 3.1; P=.01) during the initial 6-month follow-up and 2 times lower during the remainder of the 18-month follow-up. CONCLUSIONS: This intervention successfully reduced sexual risk behaviors of homeless men with mental illness. The effect diminished over 18 months but did not disappear. Similar approaches may be effective in other impaired high-risk groups.

Behavior Therapy↗
PubMed1998

Surgery in patients with hemoglobin SC disease. Preoperative Transfusion in Sickle Cell Disease Study Group.

While surgery is commonly required for complications related to hemoglobin SC (HbSC) disease, little is known about the perioperative complications or the indications for preoperative transfusion in this group. We describe the patient characteristics, preoperative transfusion regimens, and outcome in 92 patients with HbSC and sickle-variants undergoing elective surgery. Thirty-eight percent of the patients were transfused preoperatively. Patients transfused were more likely to have been hospitalized in the year prior to the surgery and scheduled for abdominal procedures. Abdominal and ear, nose and throat procedures were the most common surgeries in our study. The overall complication rate was 18% and sickle cell-related complications occurred in 9% of patients. In patients undergoing intra-abdominal procedures, the incidence of sickle cell-related complications was significantly higher in those patients not transfused prior to their surgery (35 vs. 0%). There were two deaths. We recommend selective use of preoperative transfusion in patients with HbSC disease undergoing surgery. Transfusion appears to be beneficial in abdominal cases but is not necessary with minor procedures such as myringtomy.

Adult↗
PubMed1998

Phage P22 tailspike protein: removal of head-binding domain unmasks effects of folding mutations on native-state thermal stability.

A shortened, recombinant protein comprising residues 109-666 of the tailspike endorhamnosidase of Salmonella phage P22 was purified from Escherichia coli and crystallized. Like the full-length tailspike, the protein lacking the amino-terminal head-binding domain is an SDS-resistant, thermostable trimer. Its fluorescence and circular dichroism spectra indicate native structure. Oligosaccharide binding and endoglycosidase activities of both proteins are identical. A number of tailspike folding mutants have been obtained previously in a genetic approach to protein folding. Two temperature-sensitive-folding (tsf) mutations and the four known global second-site suppressor (su) mutations were introduced into the shortened protein and found to reduce or increase folding yields at high temperature. The mutational effects on folding yields and subunit folding kinetics parallel those observed with the full-length protein. They mirror the in vivo phenotypes and are consistent with the substitutions altering the stability of thermolabile folding intermediates. Because full-length and shortened tailspikes aggregate upon thermal denaturation, and their denaturant-induced unfolding displays hysteresis, kinetics of thermal unfolding were measured to assess the stability of the native proteins. Unfolding of the shortened wild-type protein in the presence of 2% SDS at 71 degrees C occurs at a rate of 9.2 x 10(-4) s(-1). It reflects the second kinetic phase of unfolding of the full-length protein. All six mutations were found to affect the thermal stability of the native protein. Both tsf mutations accelerate thermal unfolding about 10-fold. Two of the su mutations retard thermal unfolding up to 5-fold, while the remaining two mutations accelerate unfolding up to 5-fold. The mutational effects can be rationalized on the background of the recently determined crystal structure of the protein.

Bacteriophage P22↗
PubMed1998

Language learning impairments: integrating basic science, technology, and remediation.

One of the fundamental goals of the modern field of neuroscience is to understand how neuronal activity gives rise to higher cortical function. However, to bridge the gap between neurobiology and behavior, we must understand higher cortical functions at the behavioral level at least as well as we have come to understand neurobiological processes at the cellular and molecular levels. This is certainly the case in the study of speech processing, where critical studies of behavioral dysfunction have provided key insights into the basic neurobiological mechanisms relevant to speech perception and production. Much of this progress derives from a detailed analysis of the sensory, perceptual, cognitive, and motor abilities of children who fail to acquire speech, language, and reading skills normally within the context of otherwise normal development. Current research now shows that a dysfunction in normal phonological processing, which is critical to the development of oral and written language, may derive, at least in part, from difficulties in perceiving and producing basic sensory-motor information in rapid succession--within tens of ms (see Tallal et al. 1993a for a review). There is now substantial evidence supporting the hypothesis that basic temporal integration processes play a fundamental role in establishing neural representations for the units of speech (phonemes), which must be segmented from the (continuous) speech stream and combined to form words, in order for the normal development of oral and written language to proceed. Results from magnetic resonance imaging (MRI) and positron emission tomography (PET) studies, as well as studies of behavioral performance in normal and language impaired children and adults, will be reviewed to support the view that the integration of rapidly changing successive acoustic events plays a primary role in phonological development and disorders. Finally, remediation studies based on this research, coupled with neuroplasticity research, will be presented.

Dominance, Cerebral↗
PubMed1998

Ovariectomy-induced changes in aged beagles: histomorphometry of rib cortical bone.

Bone loss associated with estrogen depletion is well documented in cancellous bone but less well characterized in cortical bone. The effects of ovariectomy on the aged beagle skeleton were studied by histomorphometric analysis of the cortical bone in sequential rib biopsies. Biopsies were taken from each ovariectomized or sham-operated dog at the time of surgery and at 1, 4, and 8.5 months after surgery. Just prior to each postoperative biopsy, tetracycline, calcein, and xylenol orange, respectively, were administered by a fluorochrome labeling procedure (2d-10d-2d) to provide markers of bone formation. Analysis of sequential rib biopsies provided a means to follow the ovariectomy response over time and to compare each animal against its own baseline. Though ovariectomy did not influence histomorphometric indices at 1 month after surgery, a transient increase in cortical bone formation occurred thereafter, with a sixfold increase over that of sham-operated dogs at 4 months (P < 0.001) and a return to near control levels at 8.5 months. Cortical porosity increased by the fourth month after ovariectomy and remained high at 8.5 months. These data demonstrate for the first time that rib cortical bone is a responsive site for the effects of ovariectomy in aged female dogs.

Aging↗
PubMed1998

High-risk characteristics of fellow eyes of patients with unilateral neovascular age-related macular degeneration.

OBJECTIVE: This study aimed to determine whether clinical tests of ocular function and macular appearance independently can help to predict which patients with unilateral neovascular age-related macular degeneration (AMD) will have a choroidal neovascular membrane (CNVM) develop in their fellow eye. DESIGN: The study design was a prospective cohort study. PARTICIPANTS: One hundred twenty-seven patients with unilateral neovascular AMD observed for up to 4.5 years participated. INTERVENTION: Functional measurements included visual acuity, macular visual field, glare recovery time, and foveal electroretinogram amplitude and implicit time. MAIN OUTCOME MEASURE: The age-adjusted proportion of patients having a CNVM develop over follow-up assessed by the Cox proportional hazards model with stepwise selection was measured. RESULTS: On average, 8.8% of patients had a CNVM develop each year. Independent risk factors for the fellow eye were its glare recovery time in minutes (relative risk = 1.30, confidence interval = 1.10-1.54, P = 0.003) and its extent of visible macular abnormalities on a four-point scale (relative risk = 1.62, confidence interval = 1.06-2.59, P = 0.03). Of the fellow eyes that converted, the interval to have a CNVM develop was inversely related to the foveal electroretinogram implicit time. CONCLUSIONS: A slower recovery from glare and more extensive funduscopic changes appear to be independent risk factors for the development of a CNVM in the fellow eyes of patients with unilateral neovascular AMD. A slower foveal electroretinogram implicit time may be a sign of early stage CNVM development, perhaps because of outer retinal ischemia. These results have clinical management implications, particularly for those patients at high risk of having a potentially treatable form of AMD develop.

Aged↗
PubMed1998

Stroke prevention trial in sickle cell anemia.

Stroke occurs in 7-8% of children with Sickle Cell Disease (Hb SS) and is a major cause of morbidity. Rates of recurrence have been reduced from 46-90% to less than 10% through chronic blood transfusions. Prevention of first stroke, however, would be preferable because even one stroke can cause irreversible brain injury. Transcranial Doppler (TCD) ultrasound can detect arterial blood flow rates associated with subsequent stroke risk. By combining TCD screening and a potentially effective treatment, first stroke may be prevented. The Stroke Prevention Trial in Sickle Cell Anemia (STOP) is the first stroke prevention trial in Hb SS and the first randomized, controlled use of transfusion in Hb SS. This multi-center trial is designed to test whether reducing sickle hemoglobin to 30% or less with periodic blood transfusions will reduce first-time stroke by at least 70% compared to standard care. Primary endpoints will be clinically evident symptoms of cerebral infarction with consistent findings on Magnetic Resonance Imaging and Angiography (MRI/MRA) or symptomatic intracranial hemorrhage. Secondary endpoints will be asymptomatic brain lesions detected by MRI in brain areas not involved in primary endpoints. The design calls for a 6-month start-up interval, 18 months of TCD screening and randomization, and observation for stroke from entry through month 54. Key features of the trial are standardized TCD and MRI/MRA protocols interpreted blindly, and blinded adjudication of endpoints. The sample size (60 per treatment group) is based on prospective data relating TCD velocity to risk of stroke. A time-averaged mean velocity of > or = 200 cm/sec is associated with a 46% risk of cerebral infarction over 39 months. The sample size is sufficient to detect 70% reduction in the primary endpoint at 90% power. This trial will determine if transfusion is effective in the primary prevention of stroke. Secondary aims may further the understanding of the effects of transfusion on the brain and guide future research into cerebrovascular disease in Hb SS.

Adolescent↗
PubMed1998

Gd-enhanced 3D phase-contrast MR angiography and dynamic perfusion imaging in the diagnosis of renal artery stenosis.

The objective of this study was to investigate the role of contrast enhancement using a three-dimensional (3D) phase-contrast (PC) magnetic resonance (MR) sequence (3D PC-MRA) and to assess the value of a dynamic MR perfusion study of the kidneys to determine the hemodynamic relevance of unilateral renal artery stenosis (RAS). Seventeen patients with unilateral RAS were examined on a standard 1.0 T imaging system using a phase shift and magnitude sensitive 3D PC sequence (TR=160 ms, TE=9 ms, venc. 30 cm/s). Following the initial pre-contrast 3D PC-MRA a dynamic first pass perfusion study was performed using a Turbo-FLASH 2D sequence (TR=4.5 ms, TE=2.2 ms, TI=400 ms) after bolus injection of 0.15 mmol gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA)/kg body weight. The 3D PC-MRA was then repeated during infusion of 0.15 mmol Gd-DTPA/kg body weight. Evaluation by three independent readers was based on maximum intensity projection images. Source images were rendered on request. Signal intensity (SI) over time curves of the renal cortex were obtained from the dynamic perfusion study and analyzed for maximum signal enhancement as well as temporal relationship to the aortic SI curve. Results from 3D PC-MRA revealed a sensitivity (pre-/post-contrast) of 100%/89%, specificity of 76%/63%, positive predictive value of 80%/69 %, negative predictive value of 90%/78%, and accuracy of 85%/75% (p=0.07). Interobserver agreement was kappa=0.61/kappa=0.47 (pre/post Gd-DTPA), respectively. Increased signal-to-noise was present in all segments of the renal arteries post contrast (p=0.0003). This came along with image degradation due to aliasing and elevated SI of venous flow that partially obscured the renal arteries. Dynamic SI curves showed a significantly decreased maximum SI in RAS (p=0.01-0.001). A temporal delay of cortical signal intensity enhancement could not be confirmed in this setting. Gd-enhanced 3D PC-MRA did not yield a superior diagnostic value in the diagnosis of RAS compared to pre-contrast measurements. Dynamic perfusion imaging of the kidneys, in combination with 3D PC-MRA, can contribute additional information in suspected unilateral RAS.

Aged↗
PubMed1998

The breast radiation injury litigation and the clinical oncologist.

A number of women with breast cancer believed they were suffering injury because radiotherapy had been given negligently. In March 1995, their solicitors were permitted by the High Court, to select 10 cases in order to further a group action. In the legal exchanges which followed, the principal issues put forward by the plaintiffs went through a number of modifications until finally, in December 1997, they were abandoned. Two cases came to trial and after a hearing of 21 days, the Judge found no negligence. Clinical oncologists should be aware of the course of the litigation and consider the lessons to be learned.

Breast Neoplasms↗
PubMed1998

Metabotropic glutamate receptor agonists potentiate cyclic AMP formation induced by forskolin or beta-adrenergic receptor activation in cerebral cortical astrocytes in culture.

The metabotropic glutamate receptor (mGluR) agonist 1-aminocyclopentane-1S,3R-dicarboxylic acid (ACPD) potentiated the accumulation of cyclic AMP induced by either beta-adrenergic receptor stimulation (isoproterenol) or direct activation of adenylyl cyclase (AC) with forskolin in rat cerebral cortical astrocytes grown in a defined medium. In contrast, ACPD inhibits the cyclic AMP response in astrocytes cultured in a serum-containing medium. Pharmacological characterization indicated that a group I mGluR, of which only mGluR5 is detectable in these cells, is involved in the potentiation of cyclic AMP accumulation. Potentiation was elicited by mGluR I agonists [e.g., (R,S)-3,5-dihydroxyphenylglycine (DHPG)], but not by mGluR II or III agonists; it was pertussis toxin resistant and abolished by procedures suppressing mGluR5 function (phorbol ester pretreatment or DHPG-induced receptor down-regulation). Nevertheless, it appears that products generated through the mGluR5 transduction pathway, such as elevated [Ca2+]i or activated protein kinase C (PKC), are not involved in the potentiation as it was not influenced by either the intracellular calcium chelator BAPTA-AM or the PKC inhibitor Ro 31-8220. An inhibitor of phospholipase C, U-73122, markedly attenuated mGluR5-activated phosphoinositide hydrolysis but did not significantly affect the DHPG potentiation of the cyclic AMP response. A mechanism is proposed in which the potentiating effect on AC could be mediated by free betagamma complex that is liberated after the agonist-bound mGluR5 interacts with its coupled G protein.

Adenylyl Cyclases↗
PubMed1998

Secondary prevention for youths living with HIV.

As the number of youths infected with HIV rises, secondary prevention programmes are needed to help youths living with HIV meet three goals: (1) increase self-care behaviours, medical adherence and health-related interactions; (2) reduce transmission acts; and (3) enhance their quality of life. This article describes an intervention programme for youths living with HIV, delivered over 30 sessions, in three modules. Based on modifications of the social action model, perceptions, attitudes and skills to enhance affective awareness and positive behavioural routines are identified as prerequisites for meeting each of the targeted outcomes. In each module, youths engage in small-group activities over 8-12 sessions with other infected peers to modify their behavioural patterns. Module 1 focuses on choosing one's social identity with respect to a seropositive status, implementing new daily routines to stay healthy, coping with receiving high quality medical care and keeping safe from reinfection. Module 2 aims to reduce substance use and unprotected sexual acts. Module 3 focuses on using sensory awareness as a strategy for enhancing the quality of life. A variety of delivery strategies are discussed for secondary interventions.

Adaptation, Psychological↗
PubMed1998

Abnormal development of biceps brachii phasic stretch reflex and persistence of short latency heteronymous reflexes from biceps to triceps brachii in spastic cerebral palsy.

Co-contraction of antagonist muscles is characteristic of spasticity arising from perinatal brain damage but not in spasticity occurring after brain damage in adulthood. Such co-contraction is a normal feature of early post-natal motor development. Heteronymous, monosynaptic Group Ia projections from biceps brachii to both the antagonist triceps brachii and to other synergist and non-synergist muscles of the upper limb occur in the newborn baby and become restricted during the first 4 years to motor neurons of primarily synergistic muscles. Longitudinal and cross-sectional studies have been performed to test the hypothesis that inappropriate heteronymous excitatory projections persist in children with perinatal brain damage who develop spasticity. Subjects with spasticity, from brain damage acquired in adulthood were also studied to determine if these projections simply become unmasked as part of spasticity, independent of the age of occurrence of the brain damage. Twenty-nine healthy newborn babies and 29 at high risk for cerebral palsy, 12 of whom developed spastic quadriparesis, were studied longitudinally for 4 years. Thirty-eight subjects, aged 8-30 years, with spasticity of perinatal origin (11 hemiplegic, 11 quadriplegic, 16 with Rett syndrome) and 11 subjects with stroke in adulthood and spastic hemiplegia were also studied. The results were compared with those obtained in 372 normal subjects aged from birth to 55 years. Small taps were delivered to the tendon of biceps brachii using an electromechanical tapper. Surface EMG was recorded from biceps and triceps brachii, pectoralis major and deltoid. In the longitudinal study, those developing spastic quadriparesis showed persistent low thresholds for the homonymous phasic stretch reflex, which had abnormally short onset latencies. There was persistence of short onset heteronymous excitatory responses in triceps brachii, while a normal pattern of restriction of heteronymous responses to pectoralis major and deltoid occurred. The same pattern was observed in older subject groups with spasticity of perinatal origin. In adults with hemiplegia following stroke the threshold of the homonymous phasic stretch reflex was low, but it had a normal onset latency. There was no evidence of abnormal heteronymous excitatory responses. In conclusion, exaggerated excitatory responses to primary muscle afferent input were observed in the homonymous (biceps brachii) and antagonist (triceps brachii) motor neurons in subjects with spasticity arising from perinatal brain damage. They are likely to play an important role in the predominant co-contraction of agonist/antagonist muscles during voluntary movement observed in subjects with spastic cerebral palsy.

Adolescent↗
PubMed1998

Speech modifications algorithms used for training language learning-impaired children.

In this paper, the details of processing algorithms used in a training program with language learning-impaired children (LLI's) are described. The training program utilized computer games, speech/language training exercises, books-on-tape and educational CD-ROM's. Speech tracks in these materials were processed using these algorithms. During a four week training period, recognition of both processed and normal speech in these children continually increased to near age-appropriate levels. We conclude that this form of processed speech is subject to profound perceptual learning effects and exhibits widespread generalization to normal speech. This form of learning and generalization contributes to the rehabilitation of temporal processing deficits and language comprehension in this subject population.

Algorithms↗
PubMed1998

Language learning impairment: integrating research and remediation.

Timing cues present in the acoustic waveform of speech provide critical information for the recognition and segmentation of the ongoing speech signal. Research has demonstrated that deficient temporal perception rates, that have been shown to specifically disrupt acoustic processing of speech, are related to specific language-based learning impairments (LLI). Temporal processing deficits correlate highly with the phonological discrimination and processing deficits of these children. Electrophysiological single cell mapping studies of sensory cortex in brains of primates have shown that neural circuitry can be remapped after specific, temporally cohesive training regimens, demonstrating the dynamic plasticity of the brain. Recently, we combined these two lines of research in a series of studies that addressed whether the temporal processing deficits seen in LLIs can be significantly modified through adaptive training aimed at reducing temporal integration thresholds. Simultaneously, we developed a computer algorithm that expanded and enhanced the brief, rapidly changing acoustic segments within ongoing speech and used this to provide intensive speech and language training exercises to these children. Results to date from two independent laboratory experiments, as well as a large national clinical efficacy trial, demonstrate that dramatic improvements in temporal integration thresholds, together with speech and language comprehension abilities of LLI children, results from training with these new computer-based training procedures.

Autistic Disorder↗
PubMed1998

A family with three germline mutations in BRCA1 and BRCA2.

Several cancer genetics centres offer testing for specific BRCA1 and BRCA2 mutations to Ashkenazi Jewish individuals with a family history of breast and ovarian cancers. Testing involves screening for three common mutations found in this population, namely BRCA1 185delAG, 5382insC and BRCA2 6174delT (Struewing et al., Nat Genet 1995: 11: 198-200; Roa et al., Nat Genet 1996: 14: 185-187; Oddoux et al., Nat Genet 1996: 14: 188-190). We have identified a large Ashkenazi Jewish kindred (W9170) with ten cases of breast cancer and four cases of ovarian carcinoma. Initially, mutation analysis for this family identified a BRCA1 185delAG mutation in the proband diagnosed with three separate primary cancers of the breast, ovary and colon. Another individual in this family diagnosed with two primary cancers of the ovary and breast, was identified as having a second mutation, BRCA1 5382insC. Subsequent work found that two sisters (cousins of the proband), both diagnosed with carcinoma of the breast, had a third mutation, BRCA2 6174delT. These three mutations have previously been found to be more common in the Ashkenazi Jewish population (References as above). The identification of all three mutations in one family, raised new implications for the manner in which testing and counselling should be offered. In our opinion, Ashkenazi Jewish individuals in breast-ovarian cancer families should be offered complete testing for the three common Ashkenazi Jewish mutations regardless of previous identification of one of these mutations in the family.

Adult↗
PubMed1998

Spastic paraplegia, optic atrophy, microcephaly with normal intelligence, and XY sex reversal: a new autosomal recessive syndrome?

Two female sibs of first cousin Iranian parents were found to have the syndrome of spastic paraplegia, optic atrophy with poor vision, microcephaly, and normal cognitive development. Karyotype analysis showed a normal female constitution in one and a male constitution (46,XY) in the other. The XY female showed normal female external genitalia, normal uterus and tubes, and streak gonads. SRY gene sequencing was normal. We conclude that the present family probably represents a new autosomal recessive trait of pleiotropic effects including XY sex reversal and adds further evidence for the heterogeneity of spastic paraplegia syndromes as well as sex reversal syndromes.

Abnormalities, Multiple↗
PubMed1998

Lead absorption and renal dysfunction in a South African battery factory.

OBJECTIVES: To test the association between inorganic lead (Pb) exposure, blood pressure, and renal function in South African battery factory workers, with both conventional and newer measures of renal function and integrity. METHODS: Renal function measures included serum creatinine, urea, and urate (n = 382). Urinary markers (n = 199) included urinary N-acetyl-beta-D-glucosaminidase (NAG), retinol binding protein, intestinal alkaline phosphatase, tissue non-specific alkaline phosphatase, Tamm-Horsfall glycoprotein, epidermal growth factor, and microalbuminuria. RESULTS: Mean current blood Pb was 53.5 micrograms/dl (range 23 to 110), median zinc protoporphyrin 10.9 micrograms/g haemoglobin (range 1.9 to 104), and mean exposure duration 11.6 years (range 0.5 to 44.5). Mean historical blood Pb, available on 246 workers, was 57.3 micrograms/dl (range 14 to 96.3). After adjustment for age, weight and height, positive exposure response relations were found between current blood Pb, historical blood Pb, zinc protoporphyrin (ZPP), and serum creatinine and urate. Blood pressure was not associated with Pb exposure. Among the urinary markers, only NAG showed a positive association with current and historical blood Pb. CONCLUSION: An exposure-response relation between Pb and renal dysfunction across the range from < 40 to > 70 micrograms/dl blood Pb was found in this workforce, with conventional measures of short and long term Pb exposure and of renal function. This could not be explained by an effect on blood pressure, which was not associated with Pb exposure. The findings probably reflect a higher cumulative renal burden of Pb absorption in this workforce in comparison with those in recent negative studies. The results also confirm the need for strategies to reduce Pb exposure among industrial workers in South Africa.

Acetylglucosaminidase↗