Period Of Time In Patients Research Articles

Improvements in breast cancer survival over time, related to adjuvant treatment and node status

Background There has been an increase in the use and effectiveness of adjuvant treatment for operable breast cancer and the aim of this study was to examine whether this has resulted in improved survival for all prognostic groups. Methods A retrospective study of 1517 patients with invasive breast cancer treated between 1980 and 2002 was carried out. The use of adjuvant treatment was compared between two time periods in patients based on nodal status, and survival was calculated by Kaplan–Meier life table analysis. Independent predictors for recurrence-free survival (RFS) were determined by Cox regression analysis. Results The use of adjuvant therapy increased for all prognostic groups. On multivariate analysis the use of radiotherapy and endocrine therapy was positively associated with RFS which was significant in the second time period. Outcome in node positive patients improved: five-year RFS from 59% to 76%, p < 0.01 and breast cancer specific survival (BCSS) from 70% to 83%, p < 0.01. However, there was no survival improvement in the larger group of node negative patients; BCSS 93% versus 95%, p = 0.99. Within the node negative group, patients with tumours ≥ 2 cm had an improved RFS from 80% to 88%, p = 0.02. Conclusion The increased use of adjuvant therapy was associated with an improved outcome in node positive patients. For node negative patients with good prognostic features the evidence of benefit was marginal.

Serum Albumin Level as a Predictor of Outcome in Traumatic Brain Injury: Potential for Treatment

Serum albumin level is correlated with outcome in various clinical situations. Albumin has multiple physiologic properties that could be beneficial in brain injury. The Lund therapy for elevated intracranial pressure uses albumin as part of its protocol and demonstrates favorable outcome. We sought to find out if albumin is associated with outcome after traumatic brain injury to justify conducting a randomized trial. A retrospective study of traumatic brain injury patients was conducted. Characteristics known to influence outcome were included in a multiple logistic regression model to analyze predictors of poor outcome at 6 months. Data were available for 138 patients. The majority of patients (65%) had a severe injury (Glasgow Coma Scale score <9). Seventy percent of patients had a favorable outcome. Albumin levels decrease considerably from normal values in the first few days after injury irrespective of outcome. Albumin remained <25 g/L for a longer period of time in patient with an unfavorable outcome (6 days vs. 3 days, p = 0.012). Multiple logistic regression analysis identified albumin levels, age, Glasgow Coma Scale score at admission, and Injury Severity Score as predictors of poor outcome. Serum albumin level seems to be an independent predictor of poor outcome. The model also identified classic predictors of poor outcome that tends to strengthen its adequacy. Because albumin level is the only modifiable factor influencing outcome, it seems justified to carry out a randomized trial of the use of albumin in the treatment of brain injury.

Patients with Positive Allergen Test have Less Favorable Outcome after Endoscopic Microdebrider-assisted Inferior Turbinoplasty

Endoscopic microdebrider-assisted inferior turbinoplasty is a newly developed surgical technique to treat patients with nasal obstruction. Although the procedure has been reported to be safe and effective, we tested the hypothesis that the prognosis might deteriorate with time in allergic rhinitis patients as identified by a positive allergen test in patients who have a persistent regional inflammation of the nose. We assessed the degree of nasal obstruction in a prospective cohort to investigate whether positive allergen test predicts outcome. In 70 consecutive patients, the symptom of nasal obstruction was evaluated subjectively by a visual analog scale (VAS) and objectively by acoustic rhinometry using cross-sectional area of the second notch (CSA-2) and nasal cavity volume before operation, and 3 months, 12 months after operation, respectively. Then, patients were classified and compared according to the multiple-antigen simultaneous test (MAST). Both MAST(+) and MAST(-) groups showed statistically significant improvement in VAS score, CSA-2, and nasal cavity volume at 12 months after operation (p < 0.01). Of note, MAST(+) patients showed less favorable results than MAST(-) patients at 12 months after operation (p < 0.05). Microdebrider-assisted inferior turbinoplasty provides effective relief for patients with nasal obstruction. However, such turbinate surgery may be successful only for a short period of time in patients with allergic rhinitis. Our finding suggests that, in selecting appropriate candidates, surgeons should consider criteria other than symptomatology, especially in patients with allergic rhinitis who may have manifestations other than at the level of the inferior turbinate contributing to nasal blockage.

Association between cancer prevalence and use of thiazolidinediones: results from the Vermont Diabetes Information System

BackgroundPeroxisome proliferator-activated receptors (PPARs) have emerged as important drug targets for diabetes. Drugs that activate PPARγ, such as the thiazolidinediones (TZDs), are widely used for treatment of Type 2 diabetes mellitus. PPARγ signaling could also play an anti-neoplastic role in several in vitro models, although conflicting results are reported from in vivo models. The effects of TZDs on cancer risk in humans needs to be resolved as these drugs are prescribed for long periods of time in patients with diabetes.MethodsA total of 1003 subjects in community practice settings were interviewed at home at the time of enrolment into the Vermont Diabetes Information System, a clinical decision support program. Patients self-reported their personal and clinical characteristics, including any history of malignancy. Laboratory data were obtained directly from the clinical laboratory and current medications were obtained by direct observation of medication containers. We performed a cross-sectional analysis of the interviewed subjects to assess a possible association between cancer diagnosis and the use of TZDs.ResultsIn a multivariate logistic regression model, a diagnosis of cancer was significantly associated with TZD use, even after correcting for potential confounders including other oral anti-diabetic agents (sulfonylureas and biguanides), age, glycosylated hemoglobin A1C, body mass index, cigarette smoking, high comorbidity, and number of prescription medications (odds ratio = 1.59, P = 0.04). This association was particularly strong among patients using rosiglitazone (OR = 1.89, P = 0.02), and among women (OR = 2.07, P = 0.01).ConclusionThese data suggest an association between TZD use and cancer in patients with diabetes. Further studies are required to determine if this association is causal.

Post-thymectomy combined treatment of prednisone and tacrolimus versus prednisone alone for consolidation of complete stable remission in patients with myasthenia gravis: a non-randomized, non-controlled study

ABSTRACTBackground: Thymectomy is a standard treatment of myasthenia gravis (MG). Immunomodulating agents are frequently given during the post-thymectomy latency period until complete remission is fully consolidated.Objective: A single-centre, non-randomized, non-controlled study was conducted to compare rates of complete stable remission (CSR) to post-thymectomy early treatment with prednisone alone or prednisone combined with tacrolimus, in 80 patients with MG.Methods: Thirty-nine consecutive patients underwent elective transsternal extended thymectomy in 1997–1999 and received prednisone alone (1.5 mg/kg/day) postoperatively, whereas 41 patients operated on in 2000–2002 received prednisone combined with tacrolimus (0.1 mg/kg per day b.i.d. starting 24 hours after thymectomy).Results: The mean follow-up was 59 months (SD 32.9) in the prednisone group and 35.9 months (SD 17.1) in the tacrolimus group ( p = 0.003). CSR was achieved in 47.5% of patients in the tacrolimus group and in 41.0% in the prednisone group ( p = 0.60). The estimated median follow-up to obtain a CSR in non-thymomatous MG was 38.2 months (95% confidence interval [CI] 30.1–46.4 months) for the tacrolimus group and 64.6 months (95% CI 50.9–78.2 months) for the prednisone group, and in patients with hyperplasia, 32.2 months (95% CI 23–41.5 months) and 62.9 months (95% CI 45.7–80.1 months), respectively (log-rank test, p = 0.03). The behavior of the two study groups stratified by thymic histology were significantly different (log-rank test, p = 0.006).Conclusions: Post-thymectomy administration of tacrolimus combined with prednisone was more effective than prednisone alone for the consolidation of CSR in a substantially shorter period of time in patients with MG.

Asthma control in patients with asthma and allergic rhinitis receiving add-on montelukast therapy for 12 months: a retrospective observational study

ABSTRACTBackground: Montelukast, a potent leukotriene receptor antagonist, is approved for treatment of both asthma and allergic rhinitis (AR). No studies to date have examined whether montelukast can improve asthma control over a long period of time in patients with seasonal AR and asthma.Objective: To evaluate asthma control and use of asthma-related medical resources by patients with inadequately controlled mild to moderate persistent asthma and seasonal AR who required addition of montelukast as part of routine care.Methods: This multicenter, 24‑month, pre–post retrospective observational study included patients receiving current inhaled corticosteroid (ICS) therapy (alone or in combination with long-acting β-agonist [LABA]), who received add-on treatment with montelukast for 12 consecutive months. The incidence of asthma attacks, defined as emergency department visit, hospitalization, or oral corticosteroid use for asthma, was compared for the year before and the year after addition of montelukast to therapy.Results: For the 696 patients from Italy, Poland, and Spain who were included in the analyses, the proportion of patients experiencing an asthma attack declined from 31.5% in the year before to 10.1% ( p < 0.001) the year after addition of montelukast to therapy. Proportions of patients with an asthma-related emergency room visit, hospitalization, and oral corticosteroid use declined from 18.7% to 3.9%, from 5.2% to 1.4%, and from 17.5% to 5.9% (all p < 0.01), respectively. The incidence of these outcomes declined in all three countries, regardless of baseline asthma severity or asthma therapy (ICS alone or ICS + LABA). Important study limitations include the possibility of selection bias or missing medical chart data in this retrospective study design. Also noteworthy is the inclusion of only those patients who remained persistent with montelukast therapy. Therefore, the results of the study are relevant for patients who remain persistent with montelukast therapy.Conclusions: Addition of montelukast to current ICS therapy improved long-term asthma control and resulted in substantial reductions in asthma-related resource use by patients with mild or moderate persistent asthma and concomitant seasonal AR who were persistent with montelukast therapy in this retrospective observational study.

Safety and tolerability of a novel chromatography‐based intravenous immunoglobulin when administered at a high infusion rate in patients with immune thrombocytopenic purpura

Intravenous immunoglobulin (IGIV) therapy is generally considered to be a safe and effective treatment for idiopathic thrombocytopenic purpura (ITP). The usual initial treatment dose is 1-2 g/kg body weight, which results in an extended infusion time, significantly impacting patients' day-to-day activities. Two crossover studies assessed the safety and tolerability of a novel IGIV preparation (IGIV-C; Gamunex, 10%) when infused at rates ranging from 0.08 mL/kg/min (the standard maximum licensed rate) to 0.14 mL/kg/min in patients with ITP. The first study included 28 patients and 3 infusion rates; 0.08, 0.11, and 0.14 mL/kg/min. The second study included 8 patients and 2 infusion rates; 0.08 and 0.14 mL/kg/min were evaluated. The incidence of infusion-related adverse events was similar for all infusion rates. Headache was the most commonly reported infusion-related adverse event. The incidence, combined for Studies 1 and 2, was 14.7% (n=34), 18.2% (n=22), and 19.4% (n=31) of patients, for each infusion rate of 0.08, 0.11, and 0.14 mL/kg/min, respectively. The majority were mild in severity. None of the other drug-related, treatment-emergent events were serious; most were mild, in spite of the higher rate of fluid loading over a shorter period of time for patients infused at 0.14 mL/kg/min. There were no clinically important changes in parameters that distinguished between infusion rates; there were no signs of hemolysis. The results suggest that IGIV-C infused at rates up to 0.14 mL/kg/min in patients with ITP is well tolerated.

Significance of laparoscopy in the management of chronic pelvic pain

Objective Chronic pelvic pain is a complex disease and is far more common than generally recognized. Study design Between 1 January 1979 and 31 December 2002 authors had performed 11,681 laparoscopic interventions. Among them, 1061 operations (9.08%) were done because of chronic pelvic pain. Results In 29.5% of these cases no anatomical abnormality was found. Analysis of data of laparoscopic operations performed from 1989 to 1990 and from 1998 to 1999 revealed that complaints dated back for a significantly longer period of time in patients presenting no obvious sign of pelvic anatomical anomaly when compared with those who had positive findings. In patients with positive pelvic findings laparotomy had previously been performed in a significantly higher number. When no apparent pelvic pathology was found medical history was also negative for ectopic pregnancy. Similarly, there were only three cases of previous adnexal operations. However, among patients with positive findings, medical history revealed 19 prior cases of ectopic pregnancy, 49 cases of previous adnexal operations, 82 appendectomy, and 26 cholecystectomy ( p < 0.01). Among patients with positive pelvic findings, diagnostic laparoscopy was immediately completed by adequate surgical treatment in the same session in more than two-third of cases. Most frequently this included adhesiolysis, ovarian cystectomy, uterosacral nerve ablation, electrocoagulation of areas of endometriosis, and ventrosuspension of the retroflected uterus. Conclusion Based on our retrospective data analysis we believe that laparoscopy is an essential method for the diagnosis and management of chronic pelvic pain.

Radical Radiotherapy For Bladder Cancer: Retrospective Analysis of a Series of 459 Patients Treated in an Italian Institution

To contribute to the available evidence about the efficacy of exclusive radiotherapy for bladder cancer through a retrospective analysis of a large series of patients consecutively treated in a single institution. A total of 459 patients with UICC categories T1-T4, N0-Nx and M0 bladder cancer consecutively treated with radiotherapy alone with radical intent formed the clinical basis for this study. Many of them (and particularly the T1 cases) had poor medical conditions or were unfit for surgery. About half of the cases (54%) had a T2 tumour, and about 18% had T3-T4 disease. Eighty per cent of the cases received minimal doses in the target volume in the range 60-70 Gy; pelvic lymph nodes were treated in 34%. Simple radiotherapy techniques were used in most cases. Average follow-up for living patients was 4.4 years. Results were analysed according to number and type of relapses: overall survival, disease-specific survival, failure-free survival probability, acute and late toxicity (RTOG scale). Actuarial 5-year overall survival, disease-specific survival and failure-free survival rates at 5 years for the entire series were 36%, 56%, 33%, respectively. Age, T category (for all the end points) and tumour dose (only for failure-free survival) were significantly related to prognosis at multivariate survival analysis. Late enteric toxicity (6.1% of the cases) was significantly linked with the treated volumes (univariate analysis). Urinary late toxicity (23% of cases) was linked with age and T category (multivariate analysis). In both cases, toxicity was mostly Grade 1 or 2. The results of radiotherapy in this negatively selected series, accrued over a long period of time in patients treated with unsophisticated techniques, are reasonably good; they add to the evidence available to support the use of modern bladder-sparing programmes, including the association of chemo- and radiotherapy.

Neurological emergencies as causes of accidents

A large number of people throughout Europe are involved in accidents every year. Neurological emergencies as the underlying cause of accidents are poorly investigated. This retrospective chart review study was performed to evaluate the incidence of such events. We retrospectively screened the records of the database of our physician-staffed emergency medical service for a 2-year period of time for patients involved in accidents suspicious of having had a neurological incident leading to the accident. The admission diagnoses of these records were compared with the final diagnosis as taken from the hospital records. Additional demographical (gender, age, time of accident) and medical (Glasgow Coma Scale, Injury Severity Score, National Advisory Committee on Aeronautics-Score) data were evaluated and analyzed. A total of 1545 records associated with accidents were screened, identifying 110 (7.1%) cases eligible for analysis. Fifty-four patients had seizure (49.1%), 7 stroke (6.3%) and 2 suffered from intracerebral hemorrhage (1.8%). The admission diagnosis made by the physician was confirmed in 91.8% of the cases. Accidents with concomitant neurological event happened significantly more frequent between 9 and 12 am. No differences were observed in demographic or medical data for patients with acute neurological event prior to the accident. Neurological emergencies, particularly epilepsy, stroke and intracerebral hemorrhage are causes of accidents which have to be considered more often than expected and happen most frequently in the morning. Other demographical and medical data provide no additional information for emergency medical personnel to specifically identify such patients. Nevertheless, emergency physicians seem to be highly skilled in finding the correct diagnosis.

Patterns of Changes in Arterial PO 2 During One-Lung Ventilation: A Comparison Between Patients With Severe Pulmonary Emphysema and Patients With Preserved Lung Function

One-lung ventilation (OLV) during thoracoscopic surgery is associated with a significant decline in arterial PO(2) in patients with severe pulmonary emphysema and patients with preserved lung function. The authors hypothesized that patterns of arterial PO(2) changes are different in these 2 patient groups. Prospective nonrandomized study. University hospital. Twenty-five patients undergoing thoracoscopic interventions: 16 with severe pulmonary emphysema and 9 patients without emphysema. Continuous arterial blood gas measurement (PaO(2), PaCO(2), pHa) during OLV of the left lung in left lateral position using the Paratrend 7 blood gas monitoring system (PT7; Pfizer Hospital Products Group, High Wycombe, UK). The decrease of PaO(2) was delayed in patients with severe emphysema. Steady state (defined as DeltaPaO(2) <7.5 mmHg/min) was reached after 18 +/- 4 minutes compared with 11 +/- 3 minutes (mean +/- standard deviation) in patients with normal lung function (p = 0.0002). PaO(2) values at steady state were comparable (p = 0.49); the pattern of changes in PaO(2) for the first 15 minutes of left-sided OLV was significantly different between the groups (p = 0.0004). The difference of predicted versus measured PaO(2) at steady state was -48 +/- 160 mmHg for patients with emphysema and -51 +/- 60 mmHg for patients with normal lung function (p = 0.019). During OLV, oxygenation is better preserved for a longer period of time in patients with severe pulmonary emphysema as compared with patients with normal lung function. In contrast to patients without emphysema, prediction of oxygenation during OLV for the individual patient with emphysema is unreliable because of large interindividual differences.

Intravenous Immunoglobulin Manufactured Using a Novel Caprylate and Chromatography-Based Method (IGIV-C, Gamunex®) Was Safe and Well Tolerated When Administered at an Increased Maximum Rate in Patients with Idiopathic Thrombocytopenic Purpura (ITP).

The objective of this study was to determine the safety and tolerability of a novel intravenous immunoglobulin preparation (IGIV-C; Gamunex®, 10%) when infused at two different infusion rates. The standard maximum licensed rate (0.08 mL/kg/min) for IGIV-C was compared with a maximum rate almost twice as high (0.14 mL/kg/min). Eight patients with a confirmed diagnosis of idiopathic thrombocytopenic purpura (ITP) were enrolled and randomized in this single center, open label, cross-over study. IGIV-C (dose 1.0 g/kg) was given on two occasions as a single daily infusion (for platelet counts <30 Giga/L), at maximum intervals of six weeks. Patients randomized to Group 1 received their first infusion of IGIV-C at the standard maximum rate; their second infusion at the higher rate. Conversely, patients randomized to Group 2 received their first infusion of IGIV-C at 0.14 mL/kg/min; their second infusion at a rate of 0.08 mL/kg/min. All infusions were started at an initial infusion rate of 0.02 mL/kg/min, with a stepwise increase to 0.04 mL/kg/min, then to 0.08 or 0.14 mL/kg/min. Infusions were maintained for at least 15 minutes at each infusion rate, and if well tolerated, increased to the target rate. All 8 patients were valid for the safety analysis. Eight patients received the standard infusion rate (0.08 mL/kg/min) and 7 patients received the faster infusion rate (0.14 mL/kg/min) (one patient did not require a second infusion due to the unexpected maintenance of platelet counts). The incidence of infusion related adverse events was similar for both infusion rates; only acetaminophen and diphenhydramine premedication were allowed. The most commonly reported adverse event was headache (62.5% of patients infused at 0.08 mL/kg/min; 57.1% at 0.14 mL/kg/min). Only headaches and urticaria were deemed by the investigator to be drug-related. None of the treatment emergent events were severe, in fact 84% were mild in nature, in spite of the difference in fluid loading over a shorter period of time for patients infused at the higher rate. Analysis of laboratory findings did not reveal any clinically important changes in parameters that distinguished between the two infusion rates, and there were no signs of hemolysis (Day 7 hemoglobin change from baseline, −0.58 ± 0.60 g/dL, 0.08mL/kg/min; and −0.99 ± 0.73 g/dL, 0.14 mL/kg/min). The mean duration of study drug infusion was 97.86 ± 6.36 minutes for the 0.14 mL/kg/min infusion rate compared with 146.25 ± 5.82 minutes for the 0.08 mL/kg/min rate, a time savings of 48.4 minutes (approximately one-third of the infusion time). These results are consistent with our previous multicenter 3-part crossover study (n = 28 patients enrolled, J Allergy Clin Immunol 2003; 111: a632). Combined, these two studies demonstrate the safety and tolerability of IGIV-C infused at rates up to 0.14 mL/kg/min for patients with ITP. The time savings associated with this faster infusion rate is likely to enhance convenience for both patient and care giver.

Fuchs’ heterochromic iridocyclitis following bilateral ocular toxoplasmosis

Purpose: To describe the development of Fuchs’ heterochromic iridocyclitis (FHI) following bilateral ocular toxoplasmosis in an Asian Indian female. Methods: Case report of a patient with bilateral ocular toxoplasmosis who developed bilateral Fuchs’ heterochromic iridocyclitis. Results: Features characteristic of bilateral Fuchs’ heterochromic iridocyclitis developed following several attacks of bilateral toxoplasmic retinochoroiditis in a 26-year-old Indian female patient. Conclusion: Fuchs’ heterochromic iridocyclitis can develop over a period of time in patients with ocular toxoplasmosis.

Retrograde holodiastolic flow in the abdominal aorta detected by pulsed Doppler echocardiography in patients with Kawasaki disease.

Retrograde holodiastolic flow in the abdominal aorta (retrograde flow) detected by pulsed Doppler echocardiography is usually noted in patients with aortic regurgitation or patent ductus arteriosus. Similar abnormal flow often is present in patients with acute phase Kawasaki Disease (KD). In 21 patients with acute phase KD, 15 had a retrograde flow. Retrograde flow was recognised in only 3 of patients with acute infection (n = 31) and in no healthy controls (n = 10). The ratio of the time velocity integral for diastolic retrograde flow to that for antegrade flow (regurgitant fraction) was significantly greater in patients with KD (median value 23%) than in patients with acute infection (1%) or healthy individuals (1%) (P < 0.001 for both). Four patients with coronary arterial involvement (one with an aneurysm and three with transient dilation of the coronary arteries) had a greater regurgitant fraction than the 17 patients without coronary arterial involvement (median values: 31% versus 18%, P < 0.05). The C-reactive protein was increased for a longer period of time in patients with KD with a greater regurgitant fraction (P < 0.01). Plasma nitric oxide (NO) metabolite concentrations were significantly greater in patients with KD than in those with acute infection or in healthy controls (P < 0.001 for both). There was a positive correlation between plasma NO metabolite concentrations and the regurgitant fraction in patients with KD (r = 0.69). Retrograde flow in the abdominal aorta is increased in patients with Kawasaki disease. Further studies are needed to clarify the causal relationship between the abnormal flow and the overproduction of nitric oxide.

Survival time in a population-based consecutive series of adult acute myeloid leukemia--the prognostic impact of karyotype during the time period 1976-1993.

A consecutive population-based series of 372 adult acute myeloid leukemias, successfully cytogenetically investigated at a single center between 1976 and 1993, is reported. All medical records were reviewed in order to ascertain the prognostic impact of karyotype, divided into three groups; favorable (t(8;21), t(15;17), and inv(16) irrespective of karyotypic complexity; n = 40), poor (der(1;7), inv(3), -5, del(5q), -7, t(9;22), and complex karyotypes including whole or partial losses of chromosomes 5 and/or 7; n = 56), and intermediate (other abnormalities or normal karyotype; n = 276). The possible modification by age, gender, time period, morphologic subtype, and bone marrow transplantation (BMT) on this prognostic impact was also determined. The chemotherapy regimens used were heterogeneous over time but principally the same at any given point in time. The majority of the patients were treated with combinations including an anthracycline and cytarabine with curative intent. Gender, morphology, and BMT did not significantly modify the effect of cytogenetic patterns on survival time, whereas age and time period did. The hazard ratios for the subgroups favorable, intermediate, and poor were 1.0, 1.2 and 1.9 at age 20-49; 1.0, 2.5 and 4.5 at age 50-64; 1.0, 4.1 and 11.4 at age 65-74; 1.0, 1.4 and 2.2 for the time period 1976-1987 and 1.0, 2.0 and 6.7 for 1988-1993. The salient feature of the Kaplan-Meier curves was the improved survival during the later time period for patients with favorable and intermediate cytogenetic abnormalities. The present findings thus suggest that it is mainly these patient groups that have benefited from advances in therapy, including supportive care.

Propylthiouracil-induced hypothyroidism reduces xenograft tumor growth in athymic nude mice

Thyroid hormones are endocrine modulators of several vital processes that are crucial to tumor growth and differentiation. Several anecdotal reports in the literature suggest that some histologic types of carcinoma may remain in a dormant state for prolonged periods of time in patients with hypothyroidism, with eventual progression of the disease once the decreased thyroid function is identified and corrected. Oral propylthiouracil (PTU) was used to induce hypothyroidism in athymic nude mice that were subsequently inoculated with lung adenocarcinoma and prostate adenocarcinoma cells. Mice were also treated with a combination of PTU and thyroxine, which resulted in hyperthyroid levels of T(4). Subcutaneous lung and prostate xenografts grew significantly more slowly in hypothyroid mice treated with PTU than in euthyroid or hyperthyroid mice, regardless of treatment with PTU. Tumors grew well in groups of mice that were changed from a hypothyroid state to a euthyroid state by withdrawal of oral PTU. Administration of PTU 3 weeks after tumor inoculation also caused the tumor growth to slow significantly compared with tumors in mice that did not receive PTU. Mice that received PTU and thyroxine had tumors that grew as well as the tumors in euthyroid control animals. Our study indicates that human lung and prostate tumors do not grow well in hypothyroid nude mice, and that rendering these animals euthyroid has a significant impact on the growth rate of these tumors. Furthermore, in vitro and in vivo data indicated that this was not a result of an interaction of the tumor cells with PTU, but rather a result of the hypothyroid state.

Propylthiouracil‐induced hypothyroidism reduces xenograft tumor growth in athymic nude mice

BACKGROUND Thyroid hormones are endocrine modulators of several vital processes that are crucial to tumor growth and differentiation. Several anecdotal reports in the literature suggest that some histologic types of carcinoma may remain in a dormant state for prolonged periods of time in patients with hypothyroidism, with eventual progression of the disease once the decreased thyroid function is identified and corrected. METHODS Oral propylthiouracil (PTU) was used to induce hypothyroidism in athymic nude mice that were subsequently inoculated with lung adenocarcinoma and prostate adenocarcinoma cells. Mice were also treated with a combination of PTU and thyroxine, which resulted in hyperthyroid levels of T4. RESULTS Subcutaneous lung and prostate xenografts grew significantly more slowly in hypothyroid mice treated with PTU than in euthyroid or hyperthyroid mice, regardless of treatment with PTU. Tumors grew well in groups of mice that were changed from a hypothyroid state to a euthyroid state by withdrawal of oral PTU. Administration of PTU 3 weeks after tumor inoculation also caused the tumor growth to slow significantly compared with tumors in mice that did not receive PTU. Mice that received PTU and thyroxine had tumors that grew as well as the tumors in euthyroid control animals. CONCLUSIONS Our study indicates that human lung and prostate tumors do not grow well in hypothyroid nude mice, and that rendering these animals euthyroid has a significant impact on the growth rate of these tumors. Furthermore, in vitro and in vivo data indicated that this was not a result of an interaction of the tumor cells with PTU, but rather a result of the hypothyroid state. Cancer 1999;86:1596–601. © 1999 American Cancer Society.

Recurrence of corneal dystrophy after excimer laser phototherapeutic keratectomy

Background Excimer laser phototherapeutic keratectomy (PTK) can be useful to treat anterior corneal dystrophies both before and after penetrating keratoplasty. Objective To evaluate the recurrence of corneal dystrophies after excimer laser PTK. Design Retrospective case series. Participants Fifty excimer laser PTK procedures were performed in 43 eyes of 33 patients with corneal dystrophies. Preoperative diagnoses included Reis-Bücklers dystrophy (13 eyes), granular dystrophy (11 eyes), anterior basement membrane (ABM) dystrophy (11 eyes), lattice dystrophy (7 eyes), and Schnyder crystalline dystrophy (1 eye). Intervention Two excimer lasers (VISX 20/20 model B and VISX Star) were used to perform all PTKs. Main outcome measures After PTK, patients were followed on a regular basis with measurement of best-corrected visual acuity and biomicroscopic examination. Evidence of recurrent dystrophy was noted according to specific criteria. Results Follow-up range was from 1.1 to 71.2 months (mean, 19.5 months). Clinically significant recurrent dystrophy occurred in 17 eyes. The ABM dystrophy recurred in the form of recurrent corneal erosions in 5 (42%) of the 12 eyes within 6 to 9 months of PTK. Four of these five eyes had mild erosions, which were treated successfully with topical medications while one eye required an additional PTK for an erosion outside the initial treatment area. Eight (47%) of 17 eyes with Reis-Bücklers dystrophy developed clinically significant recurrence an average of 21.6 months after PTK. Three (23%) of 13 eyes with granular dystrophy were found to have a significant recurrence a mean of 40.3 months after PTK. Only one (14%) of seven eyes with lattice dystrophy developed a significant recurrence at 6 months after PTK. Six eyes with significant recurrence after PTK were retreated successfully with additional PTK. Three eyes later developed recurrence of granular and Reis-Bücklers dystrophy after the second PTK. The probability of recurrence of these dystrophies after PTK was calculated using the Kaplan-Meier survival analysis. Conclusion Phototherapeutic keratectomy can restore and preserve useful visual function for a significant period of time in patients with anterior corneal dystrophies. Even though corneal dystrophies are likely to recur eventually after PTK, successful retreatment with PTK is possible.

Goniocurettage for removing trabecular meshwork: clinical results of a new surgical technique in advanced chronic open-angle glaucoma

PURPOSE: To elucidate the long-term outcome of goniocurettage as a new technique in trabecular microsurgery for advanced open-angle glaucoma. METHODS: In a prospective, nonrandomized clinical trial, 25 eyes of 25 patients with a mean age ± SD of 72.7 ± 10.1 years (range, 50 to 89 years) with uncontrolled chronic open-angle glaucoma that had undergone failed filtering procedures were treated by goniocurettage. Trabecular tissue was scraped away from the chamber angle by means of an instrument similar to a microchalazion curette (diameter, 300 μm). RESULTS: Before surgery, intraocular pressure ranged from 29 to 48 mm Hg (mean ± SD, 34.7 ± 7.1 mm Hg), and mean number of antiglaucoma medications was 2.2 ± 0.56. Follow-up averaged (±SD) 32.6 ± 8.1 months (range, 30 to 45 months). Overall success, defined as postoperative intraocular pressure of 19 mm Hg or less with one pressure-reducing agent, was attained in 15 eyes (60%), with five eyes (20%) being controlled without medication. Considering all successfully treated patients, the mean intraocular pressure was 17.7 ± 3.1 mm Hg (range, 10 to 19 mm Hg) at the final visit. Mean intraocular pressure reduction was 17.1 ± 7.1 mm Hg in these eyes, representing a net decrease from baseline of 49%. Number of antiglaucoma medications dropped to 0.63 ± 0.29. Complications included localized Descemet membrane detachment in five eyes (20%) and moderate anterior chamber bleeding in four eyes (16%). CONCLUSIONS: This new surgical technique can effectively control intraocular pressure for long periods of time in patients with open-angle glaucoma and a history of failed filtering procedures. Goniocurettage may be a suitable alternative to surgical treatment of glaucoma patients with excessive conjunctival scarification.

The value of the Health Assessment Questionnaire and special patient-generated scales to demonstrate change in systemic sclerosis patients over time.

To determine the validity and usefulness of a modified Health Assessment Questionnaire (HAQ) for measurement of disease status and changes in disease status over time in patients with systemic sclerosis (SSc). Since 1985, 1,250 patients attending the University of Pittsburgh Scleroderma Clinic have completed a modified HAQ annually. In addition to the standard HAQ questions about disability, the questionnaire includes visual analog scales (VAS) to evaluate SSc organ system symptoms, Raynaud's phenomenon, gastrointestinal (GI) tract and lung involvement, pain, and overall disease severity. In this study, the disability index (DI) (from the HAQ) and the VAS scores (on a 0-3 scale) were compared with various clinical and laboratory features recorded within 3 months of administration of the HAQ and VAS, using t-tests and Spearman's correlation tests. The HAQ DI correlated directly with skin involvement, scleroderma heart or kidney disease, tendon friction rubs, hand contractures, and proximal muscle strength. Over time, the DI correlated with changes in skin score and was a good predictor of survival. There was a significant improvement in the DI during a 2-year time period in patients treated with D-penicillamine. The VAS for digital ulcers, GI symptoms, and lung symptoms correlated very closely with subjective and objective findings for these organ systems. The presence of new digital ulcers or improvement in digital ulcers showed significant associations with the Vascular scale, new GI symptoms or improvement in GI symptoms and institution of H2-blockers showed appropriate strong correlations with the GI scale, and changes in the forced vital capacity had an excellent correlation with the Lung scale (r = 0.58, P < 0.001). By Cox regression analysis, the HAQ DI was one of the best predictors of survival. These data provide convincing evidence that a self-administered questionnaire is an accurate and inexpensive tool to measure disease status changes in SSc. Prospective studies with the HAQ administered at regular intervals, as in controlled trials, should be performed to further assess the benefits and limitations of this instrument.