Long-term bone response to particulate injectable ceramic

Flow cytometry studies of first-trimester normal human decidua have proposed that a proportion of endometrial granulated lymphocytes (eGL), the predominant leucocyte population in early human pregnancy, co-express CD69. The purpose of this study was to investigate CD69 expression by immunohistochemistry throughout the menstrual cycle and in first-trimester human decidua and to determine whether CD69 expression by eGL is an in vivo characteristic or whether the antigen is acquired in vitro after tissue disaggregation and cell purification. Single immunoenzymatic and double immunofluorescence labelling of tissue sections, supplemented with double immunoenzymatic staining of purified eGL and flow cytometry, indicated that eGL do not co-express CD69 in situ but that they acquire the molecule in vitro after cell purification and culture.     

Pharmacokinetics of oral and intravenous dolasetron mesylate in patients with renal impairment

In an open-label, randomized, two-way complete crossover study, the influence of renal impairment on the pharmacokinetics of dolasetron and its primary active metabolite, hydrodolasetron, were evaluated. Patients with renal impairment were stratified into three groups of 12 based on their 24-hour creatinine clearance (Cl(cr)): group 1, mild impairment (Cl(cr) between 41 and 80 mL/min); group 2, moderate impairment (Cl(cr) between 11 and 40 mL/min); and group 3, endstage renal impairment (Cl(cr) < or = 10 mL/min). Twenty-four healthy volunteers from a previous study served as the control group. Each participant received a single intravenous or oral 200-mg dose of dolasetron mesylate on separate occasions. Serial blood samples were collected up to 60 hours after dose for determination of dolasetron and hydrodolasetron, and urine samples were collected in intervals up to 72 hours for determination of dolasetron, hydrodolasetron, and the 5' and 6'-hydroxy metabolites of hydrodolasetron. Because plasma concentrations were low and sporadic, pharmacokinetic parameters of dolasetron were not calculated after oral administration. Although some significant differences in area under the concentration-time curve (AUC0-infinity), volume of distribution (Vd), systemic clearance (Cl), and elimination half-life (t1/2) of the parent drug were observed between control subjects and patients with renal impairment, there were no systematic findings related to degree of renal dysfunction. The elimination pathways of hydrodolasetron include both hepatic metabolism and renal excretion. Consistent increases in mean Cmax, AUC0-infinity, and t1/2 and decreases in renal and total apparent clearance of hydrodolasetron were seen with diminishing renal function after intravenous administration of dolasetron mesylate. No consistent changes were found after oral administration. Urinary excretion of hydrodolasetron and its metabolites decreased with decreasing renal function, but the profile of metabolites remained constant. Dolasetron was well tolerated in all three groups of patients. Based on these findings, no dosage adjustment for dolasetron is recommended in patients with renal impairment.     

Gamma-ray mutagen sensitivity and survival in patients with glioma

Despite advances in treatment of brain tumors, cerebral malignant gliomas are rapidly debilitating with poor survival. Patient age and tumor histology are known to influence survival in glioma patients, but these factors do not account for all of the variability in survival time. To identify additional useful predictors, we tested an assay that measures intrinsic gamma-ray mutagen sensitivity. Our hypothesis was that increased sensitivity of peripheral blood lymphocytes to chromatid breaks is associated with tumor aggressiveness and decreased patient survival. The eligible 76 patients were those with histologically confirmed malignant gliomas, seen at the University of Texas M. D. Anderson Cancer Center between 1994 and 1997, for whom we had sufficient blood for the in vitro gamma-radiation assay. After gamma-irradiation of each subject's lymphocytes, the frank chromatid breaks in 50 metaphases were averaged to calculate breaks/cell. On the basis of our patient series, we established a gamma-ray mutagen sensitivity cutoff point of 0.55 breaks/cell that was confirmed by bootstrap resampling techniques. Patients with values >0.55 breaks/cell were considered sensitive. Kaplan-Meier and Cox proportional hazards modeling were used for the analysis. The gamma-ray mutagen-sensitive patients had worse survival than the nonsensitive patients, with an unadjusted hazard rate ratio of 1.6 (95% confidence interval, 0.9-2.8; P = 0.15). After adjustment for age, tumor histology, and extent of surgical resection, the hazard rate ratio was 2.4 (95% confidence interval, 1.3-4.6; P = 0.0081). Our data suggest that gamma-ray mutagen sensitivity is a prognostic indicator of survival in glioma patients. The significance of these findings needs to be verified in studies with larger samples of patients with histologically similar gliomas.     

Metabolic response to radiation therapy in patients with cancer

The effect of radiation therapy on substrate metabolism was evaluated in five patients with head and neck or lung cancer. Stable isotope tracer methodology was used to determine urea, amino acid, glucose, and lipid kinetics during postabsorptive conditions before initiation, near the midpoint (after receiving 2,672 +/- 36 rads), and at completion (after receiving 6,072 +/- 307 rad) of a 6- to 8-week course of radiation therapy. Nutritional status was maintained throughout the treatment period by providing supplemental enteral feedings as needed. Postabsorptive plasma insulin, catecholamine, and amino acid concentrations did not change during the course of treatment. Before radiation therapy was initiated, values for the plasma rate of appearance (Ra) of urea (3.35 +/- 0.33 micromol x kg(-1) x min(-1)), alpha-ketoisocaproate ([alpha-KIC] 2.16 +/- 0.19 micromol x kg(-1) x min(-1)), phenylalanine (0.59 +/- 0.052 micromol x kg(-1) x min(-1)), and glucose (10.56 +/- 1.31 micromol x kg(-1) x min(-1)) were in the normal range. However, glycerol and palmitate Ra values (3.11 +/- 0.30 and 2.01 +/- 0.33 micromol x kg(-1) x min(-1), respectively) were 25% higher than values observed previously in normal subjects. Substrate flux did not change during radiation therapy, and measurements obtained during the midpoint and at completion of treatment were similar to initial values. These results demonstrate that large doses of radiation therapy, administered over 6 to 8 weeks to the upper body, do not cause significant metabolic stress.     

Pressor response to isometric exercise in patients with multiple sclerosis

The purpose of this study was to determine whether patients with multiple sclerosis (MS) would show attenuated heart rate and/or pressor responses to isometric handgrip exercise. Patients with MS (30 males, 74 females, aged 23-61 yr) and control subjects (9 males, 16 females, aged 25-47 yr) performed isometric handgrip exercise at 30% of maximal voluntary contraction (MVC) to fatigue. Systolic, diastolic, and mean arterial pressure (MAP) increased linearly in both groups, but were significantly lower (P < 0.05) in patients with MS at 20%, 40%, 60%, 80%, and 100% of exercise duration. Mean change in MAP at fatigue was +47.9 mm Hg for controls and +28.2 mm Hg for patients with MS, with 18 patients with MS between -6 mm Hg and +15 mm Hg. Heart rate increased normally in patients with MS. To predict change in MAP at fatigue in patients with MS, stepwise regression analysis using six variables yielded an R2 of 0.26. These data suggest that in some patients MS lesions exist in areas of autonomic cardiovascular control that result in attenuated pressor responses to exercise. In 17% of patients tested, attenuation was profound. Data also suggest an abnormal dissociation between the heart rate and pressor response to static work in patients with MS.     

Long-term use of hearing aids in patients with presbyacusis

By means of a prospective study, concerning the postoperative rate of ossification after cementless total hip replacement, it was due to prove the efficacy of radiotherapy in preventing periarticular ossification. In 1992 arthroplasty was followed by radiotherapy of 50 hip joints as regular therapy. The radiation was performed with a focal dose of 8 Gy. Patients with bilateral cementless total hip replacement and radiotherapy only at one side were of special interest in this study. Within the 24th postoperative week in 28 (56%) of the radiated hip joins no periarticular ossifications were found. In 20 (40%) we found ossifications grade 1, in 1 case ossification grade II and in 1 further case ossification grade III following the classification of Arcq. By 8 patients with former cementless total hip replacement without postoperative radiotherapy, a significant reduction of the ossification rate was found in the contralateral hip joint treated by postoperative radiotherapy. The rate of ossification was reduced by 28%. In correlation to reduction of periarticular ossification the increase on the overall range of motion in the radiated hip joins was 10.9%. By none of the patients treated by radiotherapy we found a disturbed healing process, a deep infection or an early loosening of the endoprosthesis. Postoperative radiotherapy as regular therapy for prophylaxis of periarticular ossification after Cementless total hip replacement can subsequently be recommended.     

Altered thalamic response to levodopa in Parkinson's patients with dopa-induced dyskinesias

Parkinson's disease (PD) is a progressive neurologic condition characterized by tremor, slowness, stiffness, and unstable posture. Degeneration of dopamine-producing neurons in the substantia nigra causes PD. Treatment with levodopa, a precursor of dopamine, initially ameliorates the clinical manifestations of PD. However, chronic levodopa treatment can produce severe involuntary movements (so-called dopa-induced dyskinesias or DID), limiting treatment. Pallidotomy, placement of a surgical lesion in the internal segment of the globus pallidus, reduces DID. Because this result is inconsistent with current theories of both basal ganglia function and DID, it prompted us to investigate the brain's response to levodopa. We measured regional cerebral blood flow response to levodopa with positron-emission tomography in 6 PD patients with DID, 10 chronically treated PD patients without DID, 17 dopa-na?ve PD patients, and 11 normals. The dose of levodopa was chosen to produce clinical benefit without inducing DID. This strategy allowed us to examine the brain response to levodopa across groups without the confounding effect of differences in motor behavior. We found that the DID group had a significantly greater response in ventrolateral thalamus than the other groups. This was associated with decreased activity in primary motor cortex. These findings are consistent with increased inhibitory output from the internal segment of the globus pallidus to thalamus after levodopa administration. They provide a physiological explanation for the clinical efficacy of pallidotomy and new insights into the physiology of the basal ganglia.     

The growth hormone response to hexarelin in patients with Prader-Willi syndrome

Hexarelin (Hex) is a synthetic hexapeptide with potent GH-releasing activity in both animals and men. Aim of this study was to evaluate the GH response to a maximal dose of Hex and GH-releasing hormone (GHRH) in a group of patients with Prader-Willi syndrome (PWS). Seven patients (4 boys and 3 girls, age 2.4-14.2 yr) with PWS, 10 prepubertal obese children (7 boys and 3 girls, age 7.5-12.0 yr), and 24 prepubertal short normal children (11 boys and 13 girls, age 5.9-13 yr) with body weight within +/- 10% of their ideal weight were studied. All subjects were tested on two occasions with GHRH 1-29 at the dose of 1 microgram/Kg i.v., and with Hex at the dose of 2 micrograms/Kg i.v. In the PWS patients the GH response to GHRH (peak = 6.4 +/- 2.0 micrograms/l, p < 0.0001; AUC = 248 +/- 70 micrograms min/l, p < 0.0001) was significantly lower than that observed in the short normal children and similar to that observed in the obese children. In the PWS children the GH response to Hex (peak = 7.5 +/- 1.6 micrograms/l; AUC = 309 +/- 53) was similar to that observed after GHRH and significantly lower than that observed in the obese children (p < 0.05). The results of this study show that PWS patients have a blunted GH response to the administration of a maximal dose of Hex. Whether these findings reflect a more severe pituitary GH deficiency in PWS than in obese children or a deranged hypothalamic regulation of GH secretion need further investigation.     

Neuroendocrine response in patients with uveitis

Brain imaging techniques illustrate the plastic potential even of the adult human brain in healthy subjects as in patients with peripheral or central lesions. Recovery of lost function through a persistent structural lesion in the central nervous system is accompanied by a complex and individually variable pattern of reorganisation of the brain. Changes depend on the site of the lesion and are found in both hemispheres, the damaged and the sound one within a pre-existing, widespread and bilateral organised and parallel processing network without the formation of new centres. This implies changes at rest with increased or decreased activity and altered activation patterns during performance of the restituted function. Within the primary motor system an activation at the rim of the infarct, extension into neighbouring representations, which outflow is not disturbed, altered recruitment pattern of motor cortex neurons, and recruitment of ipsilateral direct descending corticospinal tract pathways originating in the sound hemisphere are found. Disruption of the primary system leads to re-weighting of activity between the various representational levels with increased activity in secondary of higher order areas. Early sensory reorganisation indicates the potential for recovery of lost motor function. Behavioural language training in aphasics results in improvement of altered comprehension function, which is related to right hemisphere activation. Thus, reorganisation can be beneficial and training or rehabilitation influence the pattern of reorganisation.     

Long-term treatment with lansoprazole for patients with Zollinger-Ellison syndrome

BACKGROUND: Normalization of gastric secretion and cure of associated upper gastrointestinal lesions by resection of gastrinoma is possible in approximately 20% of patients with Zollinger-Ellison syndrome, leaving approximately 80% dependent on medical treatment with proton pump inhibitors for acid suppression. METHODS: Lansoprazole was given for 3-48 months (median 28 months) to 26 Zollinger-Ellison syndrome patients with peptic ulcer manifestations in all and oesophagitis in 13. Starting with 60 mg/day. the dose was individualized to lower basal acid output to less than 5 mmol/h for those with intact stomachs and less than 1 mmol/h in those who had prior gastrectomy or with oesophagitis. The patients were studied every 3 months for 1 year and then every 6 months with gastric analysis (basal and maximal acid and pepsin output) and endoscopy with biopsy for enterochromaffin-like (ECL) cells. RESULTS: Lansoprazole inhibited basal acid output by 95%, pepsin output by 65% and remained effective at the initial mean (66 +/- 4.3 mg/day) or smaller doses (56 +/- 12 mg/day) at 48 months. Mucosal lesions healed and symptoms (ulcer-type pain, diarrhoea, heartburn, weight loss) resolved rapidly, usually within a few weeks. Serum gastrin and ECL cell populations, which were elevated before treatment, remained statistically unchanged but one of the three multiple endocrine neoplasia I (MEN-I) patients developed a small carcinoid. Of the three patients with metastatic gastrinoma at diagnosis one has died and one has progressed, while the third has had stable liver metastases for 26 years. Ulcer-type relapses occurred in three of the five post-gastrectomy patients, one with fatal jejunal ulcer perforation despite adequate acid suppression. No biochemical or clinical adverse events due to lansoprazole were encountered. CONCLUSION: Lansoprazole effectively inhibits acid and pepsin secretion in Zollinger-Ellison syndrome patients without any demonstrated side-effects. Despite strict acid control, post-gastrectomy Zollinger-Ellison syndrome patients were more liable to ulcer relapse, while oesophagitis was not a marker for therapeutic difficulty.     

Humoral and cellular immune response to elastin in patients with systemic sclerosis

Fifty-six patients (age range, 15-79 yr, average, 37.0+/-18.5 yr), with a clinical and/or radiological diagnosis of acute maxillary sinusitis, were prospectively studied with ultrasound (US) and computed tomography (CT). The imaging finding which supported the diagnosis of acute sinusitis with US was the identification of the hyperechoic posterior antral wall through the hypoechoic inflammation. The findings were compared to CT (3 mm axial sections). The sensitivity of US for maxillary sinus disease was found to be 66.7% and the specificity was 94.9%, which were similar to the plain film ones (65.2 and 96.8%, respectively). The results of the present study suggest US as the method of first choice for acute sinusitis of the maxillary antra, particularly for children and pregnant women.     

Enhanced miotic response to topical dilute pilocarpine in patients with Alzheimer's disease

To determine whether miotic response to dilute (0.0625%, two drops) topical pilocarpine could be useful in detecting Alzheimer's disease (AD), we assessed the response in 14 AD patients and 10 control subjects. The miotic response to pilocarpine was significantly greater in AD patients than in control subjects (p < 0.001). In contrast, mydriatic response to the anticholinergic tropicamide (0.01%, one drop) failed to show a difference between the groups (p = 0.54). There was no significant correlation between the miotic and mydriatic responses in individuals. We conclude that dilute pilocarpine could be useful as a diagnostic tool in early AD.     

Enhanced inflammatory response to coronary angioplasty in patients with severe unstable angina

BACKGROUND: Systemic markers of inflammation have been found in unstable angina. Disruption of culprit coronary stenoses may cause a greater inflammatory response in patients with unstable than those with stable angina. We assessed the time course of C-reactive protein (CRP), serum amyloid A protein (SAA), and interleukin-6 (IL-6) after single-vessel PTCA in 30 patients with stable and 56 patients with unstable angina (protocol A). We also studied 12 patients with stable and 15 with unstable angina after diagnostic coronary angiography (protocol B). METHODS AND RESULTS: Peripheral blood samples were taken before and 6, 24, 48, and 72 hours after PTCA or angiography. In protocol A, baseline CRP, SAA, and IL-6 levels were normal in 87% of stable and 29% of unstable patients. After PTCA, CRP, SAA, and IL-6 did not change in stable patients and unstable patients with normal baseline levels but increased in unstable patients with raised baseline levels (all P<0.001). In protocol B, CRP, SAA, and IL-6 did not change in stable angina patients after angiography but increased in unstable angina patients (all P<0.05). Baseline CRP and SAA levels correlated with their peak values after PTCA and angiography (all P<0.001). CONCLUSIONS: Our data suggest that plaque rupture per se is not the main cause of the acute-phase protein increase in unstable angina and that increased baseline levels of acute-phase proteins are a marker of the hyperresponsiveness of the inflammatory system even to small stimuli. Thus, an enhanced inflammatory response to nonspecific stimuli may be involved in the pathogenesis of unstable angina.     

Immune response to anaerobic bacteria in patients with peritonsillar cellulitis and abscess

The role of four oral organisms (Fusobacterium nucleatum. Prevotella intermedia, Porphyromonas gingivalis, and Actinobacillus actinomycetemcomitans) was investigated in 19 children with peritonsillar abscess, and 17 with peritonsillar cellulitis. Antibody titers to these organisms were measured by enzyme- linked immunosorbent assay in the patient, as well as in 32 control patients. Serum levels in the patients were determined at day 1 and 42-56 days later. Significantly higher antibody levels to F. nucleatum and P. intermedia were found in the second serum sample of patients with peritonsillar cellulitis or abscess, as compared to their first sample or the levels of antibodies in controls. A total of 136 bacterial isolates, 100 anaerobic and 36 aerobic were isolated from the 19 peritonsillar abscesses. Anaerobic bacteria were found in all abscesses, and they were mixed with aerobic bacteria in 5 (26%). F. nucleatum was recovered in 14 (74%) abscesses and P. intermedia was isolated in 13 (68%). The elevated antibody levels to F. nucleatum and P. intermedia, known oral pathogens, suggest a pathogenic role for these organisms in peritonsillar infections.     

Long-term prognosis for tonsillectomy patients with IgA nephropathy

A retrospective study of 85 patients with IgA nephropathy was undertaken to determine the long-term effect of tonsillectomy. Forty-three patients (24 males and 19 females) had received tonsillectomies (Group A) and 42 patients (17 males and 25 females) had not (Group B). These patients had been followed up for more than 5 years after renal biopsy. The average age at the initial renal biopsy was 25.72 years in Group A, and 33.16 years old in Group B. The average period of renal biopsy to tonsillectomy in Group A was 10.47 months. The average follow-up period was 8 years and 9 months in both groups. At the beginning of treatment, the two groups were well matched in terms of creatinine clearance, urinalysis, and blood pressure. Six patients in Group A and eight patients in Group B were treated with steroids. The glomerular injury detected at the renal biopsy was more extensive in Group A than in Group B. Renal function in the two groups was compared. The clinical remission rate in Group A was significantly higher than in group B (P<0.05). The stable renal function rate in Group A was significantly higher than in Group B (P<0.05). The renal survival rate was 97.7% in Group A and 83.3% in Group B, but there was no significant difference between the two groups. Histologically, the rate of remission of the minor lesion in Group A was significantly higher than in Group B (P < 0.05). Our results showed that tonsillectomy for IgA nephropathy was clinically of great value.     

Enhanced calcium response to serotonin in platelets from patients with affective disorders

The additional use of the palmaris longus tendon is presented with the composite radial forearm-palmaris longus free flap, as useful for improving the final cosmetic appearance. This flap has the additional advantage of avoiding gravitational descent, which is a common problem encountered with many free flaps in head and reconstructions. A clinical case is also presented as an example of this approach.     

Diminished regional cerebral blood flow response to vibration in patients with blepharospasm

Mutations of the human Patched gene ( PTCH ) have been identified in individuals with the nevoid basal cell carcinoma syndrome (NBCCS) as well as in sporadic basal cell carcinomas and medulloblastomas. We have isolated a homologue of this tumour suppressor gene and localized it to the short arm of chromosome 1 (1p32.1-32.3). Patched 2 ( PTCH2 ) comprises 22 coding exons and spans approximately 15 kb of genomic DNA. The gene encodes a 1203 amino acid putative transmembrane protein which is highly homologous to the PTCH product. We have characterized the genomic structure of PTCH2 and have used single-stranded conformational polymorphism analysis to search for mutations in PTCH2 in NBCCS patients, basal cell carcinomas and in medulloblastomas. To date, we have identified one truncating mutation in a medulloblastoma and a change in a splice donor site in a basal cell carcinoma, suggesting that the gene plays a role in the development of some tumours.     

Long-term follow-up after subtotal parathyroidectomy in patients with renal failure

OBJECTIVES/HYPOTHESIS: The most appropriate type of surgery for hyperparathyroidism secondary to renal failure remains controversial. We report a 5-year experience of patients with hyperparathyroidism secondary to end-stage renal disease who underwent subtotal parathyroidectomy. We believe that this is the procedure of choice, offering several advantages over total parathyroidectomy with and without reimplantation. STUDY DESIGN: Retrospective review. METHODS: Review of 14 consecutive renal failure patients who underwent subtotal parathyroidectomy by one surgeon (A.K.) was performed. Follow-up ranged from 4 to 54 months. All patients were receiving chronic maintenance dialysis. All patients came to surgery with clinical symptoms of parathyroid bone disease, elevated serum calcium levels (10.1-12.4 mg/dL), and intact parathyroid hormone levels (619-4160 pg/mL), despite maximal medical therapy. At exploration four glands were identified in all patients and three and a half were removed. RESULTS: All patients experienced symptomatic relief postoperatively with normalization or near-normalization of serum calcium concentration and intact parathyroid hormone concentrations. One patient developed recurrent disease 4 months after surgery, and on re-exploration a supernumerary substernal gland was identified. A second patient developed recurrent symptoms 4 years after surgery and at the time of this writing was awaiting re-exploration. CONCLUSIONS: All patients had either resolution of or marked improvement in their subjective complaints. There have been no cases of permanent hypoparathyroidism. We believe that subtotal parathyroidectomy is the best procedure for patients with refractory symptoms of secondary hyperparathyroidism.     

Long-term survival in patients with ovarian metastases from colorectal carcinoma

BACKGROUND: It is important to clarify the relationship between the recurrent laryngeal nerve (RLN) and the ligament of Berry to prevent damage to the RLN in thyroid surgery. The purpose of the present paper is to identify this relationship to prevent surgical complications. METHODS: Among the 486 thyroid surgery cases, 689 RLNs were identified and their course detected. Topography of the laryngotracheoesophageal region and the histology of the ligament of Berry were studied in detail in 25 autopsied cadavers. RESULTS: All nerves identified by surgery and autopsy were located laterodorsally to the ligament of Berry. They were clearly separated, and no nerve penetrated the ligament nor was medially located to it. The ligament of Berry strongly connected the thyroid gland to the trachea and was identified as a whitish connective tissue band. No paralysis of the RLN occurred during identification of the nerve during surgery. CONCLUSIONS: It was confirmed that the RLN never penetrates the ligament of Berry but is located laterally to it. From these topographic findings, no injury to the RLN will occur from a separation close to the goiter in thyroid surgery.