Combination of systemic acetazolamide and topical dorzolamide in reducing intraocular pressure and aqueous humor formation

BACKGROUND: Neuroendocrine tumors commonly metastasize to the liver. Although surgical resection is considered a treatment option for patients with localized metastases confined to the liver, the longterm survival benefit of liver resection has not been clearly demonstrated. We examined the survival of patients undergoing liver resection for this disease. STUDY DESIGN: Between 1984 and 1995, we evaluated 38 patients with liver-only metastases from neuroendocrine tumors, including 21 carcinoid, 13 islet cell, and 4 atypical neuroendocrine neoplasms. Data from a combined prospective and retrospective database and a tumor registry were analyzed. Of these patients, 15 underwent complete resection of all known disease. The remaining 23 patients, who also had disease confined to the liver, had comparable tumor burden but were believed to be unresectable. The longterm survival rates of these two groups were compared. RESULTS: Patients who underwent liver resection did not differ from those who were unresectable with regard to age, pathology, primary tumor site, serum alkaline phosphatase levels, or percentage of the liver involved. All resections were complete, leaving no residual disease, and consisted of lobectomy (n = 3), segmentectomy (n = 1), and wedge resections (n = 11). There were no operative deaths. Patients who underwent hepatic resection had a significantly longer survival than unresected patients. Although median survival had not been reached in resected patients, the median survival in the unresectable group was 27 months. Patients who underwent liver resection had a higher 5-year actuarial survival (73% versus 29%). CONCLUSIONS: Hepatic resection in selected patients with isolated liver metastases from neuroendocrine tumors may prolong survival. This conclusion was reached by comparing our resected group with an unresectable group with similar tumor burden.     

Comparative evaluation of reactogenicity and immunogenicity of two dosages of oral tetravalent rhesus rotavirus vaccine. US Rhesus Rotavirus Vaccine Study Group

OBJECTIVE: To compare the safety and immunogenicity of two dosages of tetravalent rhesus rotavirus vaccine (RRV-TV) and the effect of age at dosing. METHODS: A total of 195 infants were stratified by age into 2 groups, 6 to 12 weeks and 16 to 24 weeks, and randomly assigned to receive a single dose of placebo or RRV-TV containing either 4 x 10(5) or 4 x 10(6) plaque-forming units (pfu). Symptoms were recorded for 5 days after vaccination. Anti-rotavirus IgA and neutralizing antibody to human rotavirus serotypes G1 to G4 and RRV were measured in serum obtained pre- and postvaccination. RESULTS: Rates of fever > 38 degrees C (9%), diarrhea (6%) and vomiting (8%) were similar in all groups. IgA (69% vs. 49%, P = 0.02) and RRV (85% vs. 66%, P = 0.004) seroconversion rates were significantly higher in the 4 x 10(6) pfu vaccine group as were antibody titers to RRV (440.2 vs. 263.7, P = 0.04). Older infants demonstrated significantly higher seroconversion rates and antibody titers for IgA (71% vs. 52%, P = 0.03; and 110.6 vs. 54.8, P = 0.004) and RRV (92% vs. 66%, P = 0.05 and 498.3 vs. 205.6, P = 0.01) at either dose level than did the younger infants. There were no significant differences in seroconversion rates or antibody titers to human rotavirus types G1 to G4 between the two vaccination groups. CONCLUSIONS: RRV-TV at a dose of 4 x 10(6) pfu can be safely administered to infants 6 to 24 weeks of age. A single dose of 4 x 10(6) pfu of RRV-TV was significantly more immunogenic than a single dose of 4 x 10(5) pfu but did not improve responses to the human serotypes. Older vaccine recipients demonstrated significantly higher IgA and neutralizing antibody seroconversion rates and antibody titers than younger infants independent of dosage.     

Randomized trial of the addition of gram-positive prophylaxis to standard antimicrobial prophylaxis for patients undergoing autologous bone marrow transplantation

The purpose of the study reported here was to investigate the impact of prophylaxis against gram-positive infections in patients undergoing high-dose chemotherapy and autologous bone marrow transplantation in a randomized trial. Forty-three patients undergoing high-dose chemotherapy with autologous bone marrow transplant were enrolled in a nonblinded randomized trial to receive or not to receive prophylaxis for gram-positive infections with 10(6) U of penicillin intravenously (i.v.) every 6 h (q6h) (if penicillin allergic, 750 mg of vancomycin i.v. q12h) in addition to standard antimicrobial prophylaxis with 400 mg of norfloxacin orally three times a day, 200 mg of fluconazole orally once a day, and 5 mg of acyclovir per kg of body weight i.v. q12h. The patients were being treated for germ cell cancer (n = 15), breast cancer (n = 16), Hodgkin's disease (n = 3), non-Hodgkin's lymphoma (n = 4), acute myeloid leukemia (n = 1), acute lymphoblastic leukemia (n = 1), and ovarian cancer (n = 3). The trial was stopped because of excess morbidity in the form of streptococcal septic shock in the group not receiving gram-positive prophylaxis. There were significantly fewer overall infections (10 versus 3; P = 0.016) and streptococcal infections (9 versus 1; P = 0.0078) in the group receiving gram-positive prophylaxis. There were no significant differences in the numbers of deaths, duration of broad-spectrum antibiotics, or incidence of neutropenic fever between the two groups. Prophylaxis for gram-positive infections with penicillin or vancomycin is effective in reducing the incidence of streptococcal infections in patients undergoing high-dose chemotherapy and autologous bone marrow transplant. However, this approach may carry a risk of fostering resistance among streptococci to penicillin or vancomycin.     

Arthroscopic release for chronic, refractory adhesive capsulitis of the shoulder

Idiopathic adhesive capsulitis usually responds to gentle physical therapy or, if that fails, to closed manipulation with the patient under anesthesia. In some patients, however, loss of motion may be refractory to either of these treatments and an operative release may be indicated. We are reporting on the technique and results of arthroscopic capsular release as a new alternative for the management of such patients. During a three-year period, we managed twenty-three patients who had idiopathic adhesive capsulitis that had failed to respond to physical therapy or closed manipulation. These patients had an arthroscopic anterior capsular release and received forty-eight hours of intensive physical therapy as inpatients. During the physical therapy, the patients received an interscalene regional analgesic with use of repeated nerve blocks or with a continuous infusion through an interscalene catheter. This was followed by a supervised outpatient physical-therapy program. Six patients also had an arthroscopic acromioplasty for the treatment of impingement. There were no complications related to any of the procedures. At a mean of thirty-nine months (range, twenty-four to sixty-four months) after the arthroscopic procedure, the improvement in the score of Constant and Murley averaged 48 points (range, 13 to 77 points). The mean improvement in motion was 49 degrees (range, 0 to 105 degrees) for flexion; 42 degrees (range, 10 to 80 degrees) and 53 degrees (range, 0 to 100 degrees) for external rotation in adduction and abduction, respectively; and eight spinous-process levels (range, three to fourteen levels) and 33 degrees (range, 30 to 60 degrees) for internal rotation in adduction and abduction, respectively. These gains in motion were all significant (p < 0.01) compared with the preoperative values and were within a mean of 7 degrees of the values for the contralateral, normal shoulder. We concluded that, in patients who have loss of motion that is refractory to closed manipulation, arthroscopic capsular release improves motion reliably with little operative morbidity.     

The Glu318Gly mutation of the presenilin-1 gene does not necessarily cause Alzheimer's disease

In early-onset familial Alzheimer's disease (AD) pathogenic mutations have been found in the amyloid precursor protein (APP) gene and in the presenilin (PS)-1 and PS-2 genes. We screened for mutations in these genes in 20 patients with familial AD from the Finnish population. In addition, we sampled 41 sporadic AD patients and 59 controls to test for mutations identified in our familial AD cases. We detected an A-to-G transition in the PS-1 gene, resulting in a glutamic acid (Glu)-to-glycine (Gly) substitution at codon 318 in 2 familial and 2 sporadic AD patients. The Glu318Gly mutation has previously been reported to cause AD. We also found the Glu318Gly mutation in 4 healthy aged controls (range, 74-87 years). We thus conclude that the mutation is most likely a rare polymorphism not related to AD.     

Addisonian crisis provoked by levothyroxine substitution therapy

A women aged 36 with a positive family anamnesis for autoimmune endocrine diseases and a history of thyroid diseases, developed major complaints of general malaise, orthostatic hypotension and loss of appetite after the start of a treatment with levothyroxin because of (sub)clinical hypothyroidism. She was found to suffer from primary adrenocortical insufficiency masked by excessive use of liquorice and a lowered metabolism, but which via the suppletion with thyroid hormone had led to an addisonian crisis.     

Hepatic failure and liver cell damage in acute Wilson''s disease involve CD95 (APO-1/Fas) mediated apoptosis

We gave auditory examples of two semantic categories through headphones to 100 surgical patients anaesthetized with propofol and enflurane. This presentation was made during certain stages of the procedure, potentially associated with arousal, and during steady-state anaesthesia. Postoperative review using category generation tests showed successful priming in a pre-induction group but no evidence of implicit memory in the anaesthetized groups. These results suggest that timing an auditory input to coincide with surgical stimulation does not increase the probability of retrieval of information by this type of testing.     

Influence of fathers' social class on cardiovascular disease in middle-aged men

BACKGROUND: The independent effect of early life circumstances on adult cardiovascular risk is still unresolved. We assessed the associations of father's social class with cardiovascular risk factors and with risk of ischaemic heart disease and stroke in adult life. METHODS: We did a longitudinal study of cardiovascular disease in 5934 men aged 40-59 years at enrollment. A cross-sectional measurement survey was done between 1978 and 1980 and a follow-up questionnaire was completed in 1992. The main endpoints were non-fatal myocardial infarction and stroke based on general practitioners' reports obtained between screening and 1992 and on recall of physician-diagnosed ischaemic heart disease in the 1992 questionnaire. FINDINGS: Father's social class was strongly associated with social class in adulthood (fathers' occupation was manual for 41.3% of professionals [I] vs 89.1% for unskilled manual workers [V]) and was significantly related to height (non-manual vs manual 175.4 cm [SE 0.2] vs 172.9 cm [0.1], p < 0.0001) and obesity (213 [14.1%] vs 804 [20.1%], p < 0.0001) irrespective of adult social class; no association was found with blood glucose (log, 1.69 [0.005] vs 1.70 [0.003], p = 0.22) or cholesterol (6.34 [0.03] vs 6.29 mmol/L [0.02], p = 0.16. Men whose fathers' social class was manual had significantly higher rates of non-fatal myocardial infarction (342/4006 vs 92/1510) and self-reported physician-diagnosed ischaemic heart disease (686/4006 vs 192/1510) than men whose fathers' social class was non-manual, even after adjustment for adult social class and other established risk factors (relative odds 1.3 [95% Cl 1.0-1.7], p < 0.05 and 1.3 [1.1-1.6], p < 0.01, respectively). The influence of father's social class on non-fatal myocardial infarction and ischaemic heart disease was only seen in men whose adult social class was non-manual. No association was seen between father's social class and non-fatal stroke. INTERPRETATION: Father's social class is strongly associated with adult social class. The higher risk of non-fatal myocardial infarction and self-reported physician-diagnosed ischaemic heart disease seen in men whose father's social class was manual suggests that socioeconomic status early in life has some persisting influence on ischaemic heart disease risk in adult life.     

Chromosome-specific aneusomy in carcinoma of the breast

Fluorescence in situ hybridization was performed on touch preparations from 55 primary infiltrating ductal carcinomas of the breast to determine numeric chromosome abnormalities. The frequency of aneusomy, measured by both nondisomy and chromosomal gain, was determined for chromosomes X, 4, 6-12, 17, and 18 with the use of chromosome-specific, alpha-satellite DNA probes. The presence of chromosome-specific numeric abnormalities was correlated with established clinicopathological parameters, including tumor size, lymph node involvement, tumor grade, estrogen receptor level, and menopause status. In addition, a case-control study was performed to explore a possible association between chromosome-specific aneusomy and recurrence in lymph-node-negative patients. Although chromosomes 8 and 6 were most frequently aneusomic, numeric abnormalities of chromosomes 4 and 11 were most strongly associated with established prognostic factors. For chromosomes 4 and 11, strong associations were found with tumor involvement of lymph nodes and increased tumor size, along with a weaker association with tumor grade. In addition, numeric abnormalities of the following chromosomes were associated with the corresponding prognostic factors: chromosomes X, 7, and 12 with lymph node status; chromosomes 10, 17, and 6 with tumor size; and chromosomes 7, 12, 17, and X with tumor grade. No correlations were observed with estrogen receptor level or menopause status. In the case-control study performed on isolated nuclei of paraffin-embedded tissue from lymph node-negative breast cancer patients (19 cases and 19 controls), the gain of chromosome 4 was correlated with disease progression. These findings suggest that chromosome-specific aneusomy is associated with certain established prognostic factors and may be associated with disease progression.     

Radiolabelled antimicrobial peptides for imaging of infections: a review

Risk factors suggestive of relatively late exposure to EBV have been consistently associated with Hodgkin's disease (HD) in younger adults. In addition, evidence of EBV infection has been found in the Reed-Sternberg cells themselves in about one-third to one-half of all HD cases. However, no study yet published has correlated these childhood social environment risk factors with the presence of EBV in Hodgkin's tumor cells. We examined whether EBV-positive HD occurs in those patients whose childhood environment would predispose them to relatively late exposure to EBV. The study population consisted of 102 cases of mixed cellularity (MC; n = 25) or nodular sclerosing (n = 77) HD. Samples that tested positive for either EBV-encoded RNA or latent membrane protein or both were considered EBV-positive. Of the 102 cases, 83 completed a questionnaire regarding childhood social environment. The association with EBV-positivity was estimated by the odds ratio (OR) with 95% confidence intervals (CI). Twenty-two percent of the cases were EBV-positive. These cases were more likely to be MC (OR, 6.2; CI, 2.3-16.3) and male (OR, 3.4; CI, 1.3-9.0). History of infectious mononucleosis (IM) was not predictive of EBV-positivity, with only 3 of 14 such patients being EBV-positive (P = 0.82). Contrary to our hypothesis, no association between EBV and childhood environment risk factors was identified. The association of EBV with MC histology and male gender agrees with previous reports. The most intriguing finding was the dissociation between IM history and EBV-positivity, in that almost all of the cases with a history of IM were EBV-negative.