Search PubMed⌕ Search

Biomedical subjects

R Grossman

Publications and source records attributed to R Grossman.

At least 73 records · Page 4Linked to original sources

Efficacy and safety of oral cyclosporin A (CyA; Sandimmun) for long-term treatment of chronic severe plaque psoriasis.

The value of oral cyclosporin A (CyA; Sandimmun) in the treatment of chronic severe plaque psoriasis has already been established. Many controlled studies have addressed the issues of efficacy and safety, mostly in studies of several months duration. Patients treated for up to several years have been reported, but never in multicentre controlled studies. Guidelines have established the maximum dose permissible to reduce the risk of side-effects. However, the efficacy and safety of therapy of longer duration remain under investigation. The results of a multicentre prospective randomized clinical study (251 patients) to evaluate the efficacy, safety and tolerability of two dose levels of CyA (2.5 or 5 mg/kg/day) for inducing remission, and for use in long-term maintenance therapy for up to 21 months, are presented. An assessment of relapse as the dose was tapered (during the last 3 months of treatment), and the reversibility of CyA-induced side-effects, is also presented (follow-up phase of 3 months). Efficacy was evaluated by means of the psoriasis area and severity index (PASI). Safety was assessed by using the results of vital signs, physical examination, laboratory tests and physician and patient evaluation of adverse events. During the induction of remission phase of therapy, a total of 184 patients (73%) were treated successfully. The percentage of patients classified as successes at the end-point was significantly higher in the group on 5.0 mg/kg/day (92%) than in that on 2.5 mg/kg/day (52%; P < 0.001). A total of 215 (86%) patients reported at least one adverse event during the study. In 136 patients (54%) the reported adverse event was judged by the investigator as being related to CyA. Nineteen patients (8%) reported events that were judged as severe, and related to treatment with CyA. A total of 45 patients (18%) discontinued treatment due to adverse events. Hypertension was one of the reasons, or the reason, for discontinuation in 16 patients (6%). The occurrence of hypertension appeared unrelated to CyA dose. One hundred and sixteen patients (46%) experienced a maximum increase in serum creatinine > 30% above baseline values on at least one occasion. This increase in serum creatinine was often transient, and was one of the reasons, or the reason, for discontinuation in 24 patients (10%). An increase in serum creatinine > 30% above baseline was dose-related. The results of this study show that 5.0 mg/kg/day of CyA is significantly more effective than 2.5 mg/kg/day in the treatment of chronic plaque psoriasis.(ABSTRACT TRUNCATED AT 400 WORDS)

Administration, Oral↗

Clinical subtypes of schizophrenia: differences in brain and CSF volume.

OBJECTIVE: Investigations of the relation of clinical features of schizophrenia to neuroanatomic measures have produced inconclusive results. The purpose of this study was to examine measures of whole-brain volume in men and women and relate them to clinical subtypes of schizophrenia. METHOD: Magnetic resonance imaging measures of cranial, brain, and ventricular and sulcal CSF volume were examined in 81 patients with schizophrenia (50 men and 31 women), divided into subgroups based on their symptom profiles, and 81 demographically matched healthy comparison subjects. RESULTS: The men had higher cranial and brain volumes than the women. The patients had smaller cranial and brain volumes than the comparison subjects; they also had higher ventricular CSF volumes and thus higher ventricle-brain ratios (VBRs). Ratio elevations were larger for the female than for the male schizophrenic patients. The patients with predominantly negative symptoms of schizophrenia had higher VBRs and sulcal CSF-brains ratios than the comparison subjects, although the component volumes did not differ. The patients with predominantly Schneiderian symptoms had higher VBRs than the comparison subjects but showed reduced cranial and brain volumes. The paranoid patients had normal VBRs, reduced sulcal CSF-brain ratios, and lower cranial and sulcal CSF volumes. CONCLUSIONS: The results suggest two patterns of neuroanatomic whole-brain abnormalities that differ in severity according to the relative prominence of negative, Schneiderian, and paranoid symptoms. These patterns may reflect differential involvement of dysgenic and atrophic pathophysiological processes. Sex moderates abnormalities in the neuroanatomic features of schizophrenia.

Adolescent↗

Chromametric quantification of pigmentary changes in the solar lentigo after sunlight exposure.

The purpose of this study is to compare by chromametric analysis the changes seen in normal skin and solar lentigos after exposure to sunlight. The color measurements were made with a Minolta CR200 chromameter and expressed in the L*a*b* system, which allows a color to be quantified according to 3 axes: white-black (L*), red-green (a*) and yellow-blue (b*). In order to better assess the sensitivity of physiological mechanisms involved in this pigmentation, we chose the weakest conditions of sunlight: the first series of measurements were made at the end of the winter (March) on areas rarely exposed for several months, and the second measurement was made 2 months later before the first intense summer solar exposure. Solar lentigos underwent a significant change in pigmentation, with a darkening of these lesions and an increase in the red and yellow color components. The pigmentation of healthy skin adjacent to these lentigos remained unchanged.

Adult↗

Additive effects of calcipotriol and cyclosporine A: from in vitro experiments to in vivo applications in the treatment of severe psoriasis.

We report that calcipotriol (CPT) is a potent inhibitor of lymphocyte proliferation in mixed epidermal cell lymphocyte reactions. In this model, CPT and cyclosporine A (CsA) have synergistic effects. These results have led to a randomised double-blind therapeutic study protocol in patients with severe psoriasis. In these patients, topical CPT and sub-therapeutic doses of CsA (2mg/kg/d) induce disappearance of cutaneous lesions. This therapeutic association may minimize secondary side effects of both drugs.

Adult↗

An objective assessment of treatment for orbital hypertelorism.

A retrospective statistical analysis of orbital hypertelorism correction was performed by comparing the preoperative and postoperative intercanthal distances of these patients with published age-matched normal values. Forty-five patients who had undergone surgery over a 15-year period with an average follow-up of 5 years (6 months to 14 years) were evaluated. Comparison of age-normalized preoperative and postoperative intercanthal distances revealed a significant difference for orbital hypertelorism patients as a group (p < 0.0001), patients with clefts (p < 0.0001), patients with nasoencephalocele (p < 0.01), and patients with frontonasal dysplasia (p < 0.05), but not for those patients with craniofacial dysostosis (p < 0.20). Multiple analyses of variance revealed a significant interaction existing between the extent of preoperative deformity and the cause of hypertelorism for both the postoperative deformity and the total amount of correction achieved, but not for the type of surgery or for the age at which the surgery was performed.

Analysis of Variance↗

The surgical management of orbitofacial dermoids in the pediatric patient.

Orbitofacial dermoids in the pediatric population represent a diverse group of lesions. Because of their variability in both clinical presentation and contiguous structure involvement, a thorough understanding of their surgical-pathologic anatomy is imperative. In this retrospective review of 84 lesions in 84 patients, we noted segregation of the lesions into three distinct subgroups: brow region dermoids, orbital region dermoids, and nasoglabellar dermoids. Further, we identified physical characteristics within each subgroup that appeared to direct diagnostic workup and subsequent surgical intervention. From this experience, a treatment algorithm was developed that gives the practitioner more precision in the management of these lesions.

Algorithms↗

The restaging of responding patients with limited small cell lung cancer. Is it really useful?

A retrospective review of data on patients entered on two limited small cell lung cancer studies of the National Cancer Institute of Canada (BR.3 and BR.6) was undertaken to determine the value of restaging and rebronchoscopy in responding patients. An economic evaluation was also done. Repeat scans (brain, liver) and bronchoscopy were carried out in 190 patients and 5 (2.6 percent) were positive, despite other evidence suggesting response. One hundred thirty-nine of 324 patients who achieved complete response on the two trials underwent rebronchoscopy. Among these, 122 (87.7 percent) were negative and eight (5.8 percent) were inconclusive. Nine (6.5 percent) were positive despite other evidence suggesting the patient had achieved a complete response. A small group of nine patients with positive rebronchoscopy survived for a shorter time than the group with negative or inconclusive rebronchoscopies. The survival difference was only statistically significant when analyzed using the log rank test, but it was not significant when analyzed by the Wilcoxon test. The economic analysis showed that it costs $11,333 per patient reclassified when scans were redone in these patients. The cost could even have been higher had we used present-day scanning techniques (computed tomography and magnetic resonance imaging), although they might be slightly more sensitive. The cost of rebronchoscopy per patient reclassified was $14,960. Therefore, we recommend that restaging (scans or rebronchoscopy) not be done in responding patients with limited small cell lung cancer, thus potentially saving health care dollars as well as reducing patient inconvenience with no detrimental effect on survival.

Bronchoscopy↗

Persistent acantholytic dermatosis: sex-related differences in clinical presentation?

We report the case of a 58-year-old man with a chronic papular eruption of 10 years' duration. Histopathology revealed focal acantholytic dyskeratosis. This condition is thought to represent a distinct entity which has been reported under several names and frequently referred to as persistent acantholytic dermatosis. The relationship between this condition and transient acantholytic dermatosis (Grover's disease), emphasizing sex-related presentations, is discussed.

Acantholysis↗

Age-related changes of the craniofacial skeleton: an anthropometric and histologic analysis.

With the development of increasingly sophisticated methods for the alteration of bony facial form consequent to age, it is imperative that the surgeon have a fundamental knowledge of the age-related changes the skeleton may undergo. To understand these changes better, a detailed anthropometric and histomorphic analysis of the craniofacial skeleton as a function of age was undertaken. The study consisted of a detailed craniometric analysis of 160 skulls selected randomly from a Caucasian population of skeletal remains totaling 1500 specimens. Additionally, a histologic analysis of the supraorbital ridge in a separate preserved cadaver population was performed. Although the results showed individual variation as expected, definite changes in craniofacial morphology were observed. These included (1) appreciable reduction of facial height, most marked in the maxilla and mandible, and strongly correlated with loss of teeth, (2) modest increase in facial width, (3) modest increase in facial depth, except in those regions associated with tooth loss, and (4) general coarsening of bony prominences. Histomorphic analysis demonstrated increasing porosity with age, more marked in the female population. Although these changes represent population trends, in any given patient, any or all of them may be present to varying degrees. Surgeons should be aware of these possibilities and consider selective alterations of the skeletal foundation, either separately or in concert with the overlying soft-tissue envelope, in order to optimize the results of surgery for the aging face.

Adult↗

Hypercapnic ventilatory response in recipients of double-lung transplants.

Ten survivors of double lung transplantation using a tracheal anastomosis underwent assessment of their ventilatory responses to hypercapnia (HCVR) at least 3 months postsurgery. At the time of HCVR testing, pulmonary functions were normal in four and abnormal in six patients who demonstrated degrees of obstruction, restriction, or mixed defects. Arterial blood gas measurements were normal. Postoperatively, hypercapnic responses were low or low normal. Mean changes in tidal volume and mean change in respiratory frequency in response to hypercapnia postoperatively were not different in patients with normocapnic versus hypercapnic preoperative blood gases. Neither postoperative resting PCO2 nor muscle strength (as measured by MIP) were predictive of the degree or character of the patients' ventilatory responses to hypercapnia. The factors resulting in the observed blunting of the hypercapnic response in this denervated population require further clarification; however, comparison of data between this patient population and recipients of heart-lung transplantation reported elsewhere suggests that alterations in pulmonary function correlate with the observed depression in HCVR.

Carbon Dioxide↗

Adult T-cell leukemia/lymphoma presenting as an acute noninfectious pneumonitis.

A 29-year-old man presented with a four-week history of pneumonic symptoms and progressive roentenographic infiltrates which were unresponsive to orally administered antibiotics. Bronchoscopy failed to identify an infectious etiology, but abundant atypical lymphocytes in the bronchial washings were present. A diagnosis of adult T-cell leukemia/lymphoma was subsequently made. After administration of cancer chemotherapy, the pneumonic symptoms and chest roentgenogram infiltrates resolved. This report suggests that ATL can present as an acute noninfectious pneumonitis.

Acute Disease↗

Renal transplantation at the University of Pennsylvania Medical Center: an update of results in the cyclosporine era.

This chapter presents a summary of living-related, living-unrelated, and cadaver renal transplantation performed at the University of Pennsylvania Medical Center between January 1984 and October 1992. Over the past 9 years, 895 patients (557 males, 338 females, mean age 42 yrs) received 942 renal transplants; 599 patients received kidneys from cadaver donors (n = 627) and 296 patients received kidneys (n = 315) from living donors of all types. During this period, 151 patients were retransplanted, sometimes more than once (159 total retransplants, 124 secondary grafts, and 35 third or more transplants). An analysis of patient ant graft survival rates (calculated by actuarial methods) for different categories of transplant recipients was performed. Black recipients, as a racial subcategory, had the poorest graft outcome, especially when followed over the long term. Graft survival rates for Black recipients who were retransplanted with cadaver grafts were even worse and were noted to be similar to the diabetic population that received cadaver retransplants (66% vs 62% at 1 yr and 32% vs 25% at 5 yrs). Diabetic recipients of living-donor transplants had excellent graft survival results, similar to nondiabetic, living-donor recipients (patient survival rates 98% and 92% vs 97% and 92% at 1 and 5 yrs; graft survival rates 92% and 82% vs 92% and 82% at 1 and 5 yrs). HLA-identical recipients of first cadaver grafts demonstrated the best outcome in the entire cadaver series (graft survival rates 91% and 83% at 1 and 5 yrs, respectively). HLA-identical recipients of second or more cadaver grafts had poorer results than expected (50% graft survival at 1 yr) despite a 100% patient survival rate. HLA-identical recipients of living-related grafts had the best graft survival rates (96% at 1 yr and 94% at 5 yrs) and superior graft survival rates for retransplanted grafts as well (100% at 1 and 5 yrs). We conclude that in the last decade, patient and graft survival rates for cadaveric and living-donor renal transplants have improved dramatically relative to the results obtained in the pre-CsA era. Long-term graft survival in Black recipients remains lower than in other races, suggesting the need to analyze other factors to explain poorer graft survival in this recipient population. Results in diabetic recipients continue to be excellent at our center, encouraging the continuation of our aggressive approach to try to transplant diabetics as early as possible, particularly when a living donor is available.

Academic Medical Centers↗

Gender differences in age effect on brain atrophy measured by magnetic resonance imaging.

A prospective sample of 69 healthy adults, age range 18-80 years, was studied with magnetic resonance imaging scans (T2 weighted, 5 mm thick) of the entire cranium. Volumes were obtained by a segmentation algorithm that uses proton density and T2 pixel values to correct field inhomogeneities ("shading"). Average (+/- SD) brain volume, excluding cerebellum, was 1090.91 ml (+/- 114.30; range, 822.19-1363.66), and cerebrospinal fluid (CSF) volume was 127.91 ml (+/- 57.62; range, 34.00-297.02). Brain volume was higher (by 5 ml) in the right hemisphere (P less than 0.0001). Men (n = 34) had 91 ml higher brain and 20 ml higher CSF volume than women (n = 35). Age was negatively correlated with brain volume [r(67) = -0.32, P less than 0.01] and positively correlated with CSF volume (r = 0.74, P less than 0.0001). The slope of the regression line with age for CSF was steeper for men than women (P = 0.03). This difference in slopes was significant for sulcal (P less than 0.0001), but not ventricular, CSF. The greatest amount of atrophy in elderly men was in the left hemisphere, whereas in women age effects were symmetric. The findings may point to neuroanatomic substrates of hemispheric specialization and gender differences in age-related changes in brain function. They suggest that women are less vulnerable to age-related changes in mental abilities, whereas men are particularly susceptible to aging effects on left hemispheric functions.

Adult↗

Effect of Towne live virus vaccine on cytomegalovirus disease after renal transplant. A controlled trial.

OBJECTIVE: To test the efficacy of vaccination with the Towne live attenuated cytomegalovirus vaccine. DESIGN: A double-blind, randomized, placebo-controlled trial in candidates for renal transplantation. The cytomegalovirus serologic status of both recipients and donors were determined, and the recipients were followed for periods of 6 months to 7 years after transplant. SETTING: A university transplant center. PATIENTS: The analyses were made on 237 patients who were given either vaccine or placebo, received renal transplants, and were followed for at least 6 months. INTERVENTION: Subcutaneous inoculation with Towne live attenuated virus or with placebo. MAIN OUTCOME MEASURES: The presence of cytomegalovirus infection was defined by virus isolation and antibody tests. If infection occurred, a prearranged scoring system for cytomegalovirus disease was used to objectify disease severity. RESULTS: The vaccine was well tolerated, and there were no discernible long-term adverse effects. Recipients who were originally seropositive did not clearly benefit from vaccination. Protective efficacy was analyzed in the group at highest risk for cytomegalovirus disease; recipients who were seronegative at the time of vaccination and who received a kidney from a seropositive donor. Compared with placebo recipients, vaccinated patients in this group had significantly less severe cytomegalovirus disease, with a significant reduction in disease scores (P = 0.03) and 85% decrease in the most severe disease (95% CI, 35% to 96%), although infection rates were similar. Graft survival at 36 months was improved in vaccinated recipients of cadaver kidneys (8 of 16) compared with unvaccinated recipients (4 of 16) (P = 0.04). CONCLUSIONS: Previous vaccination of seronegative renal transplant recipients with live cytomegalovirus results in reduction of disease severity mimicking the action of naturally derived immunity.

Adult↗

Magnetic resonance imaging in schizophrenia. I. Volumetric analysis of brain and cerebrospinal fluid.

The study reports magnetic resonance imaging data for 42 patients with schizophrenia and 43 normal controls. Volumetric measures were obtained with a validated computerized algorithm for segmentation of cranial volume into brain tissue and central and peripheral cerebrospinal fluid (CSF), with high inter-operator reliability. Patients did not differ significantly in whole-brain volume, but had higher whole-brain CSF volume and higher ratios of ventricular and sulcal CSF to cranial volume. Covarying age and education did not affect the differences. However, there was considerable overlap both in CSF volumes and in volume-cranium ratios, and most patients were within the normal range. This suggests that anatomic changes reflected in CSF can provide a limited substrate for schizophrenia and may apply only to subpopulations. Although there was no gender x diagnosis interaction, the results for sulcal CSF were significant only for men, whereas for women, the ventricular ratios were marginally higher in patients.

Adolescent↗