Intracytoplasmic sperm injection in the mouse

Intracytoplasmic sperm injection (ICSI) into mouse oocytes involvesa very low survival rate. This study was designed to determinewhy ICSI frequently fails in mice. Metaphase II oocytes wereobtained from superovulated 4–6 week old F₁ hybrid mice.Spermatozoa were retrieved from the epididymis of 12–14week old F₁ hybrid mice. The spiked microinjection pipette usedto inject a spermatozoon into the ooplasm had outer and innerdiameters of 10 and 8 µm respectively. The oocytes usedin the first part of the study were not activated (group 1).Some oocytes were incubated with calcium ionophore for 5 min(group 2). The injected oocytes were evaluated 6, 20, 48 and72 h after injection. A total of 143 eggs in each group underwentICSI. In group 1, sperm heads escaped into the perivitellinespace. In all, 63 (47%) of the remaining oocytes were damagedduring the injection or had degenerated by the first evaluation.The survival rate was 53%, but fertilization did not occur.In group 2, 31 oocytes (22%) were damaged during microinjectionor soon degenerated. Two oocytes underwent accidental subzonalinsemination. Six oocytes were fertilized (4.2%) among the 78%of survivors. After injection, the sperm tail was found in thecytoplasm (27 and 31% in groups 1 and 2 respectively), the perivitellinespace (45% in both groups) or protruding through the zona pellucida(28 and 23% respectively). More oocytes degenerated when thetail remained in the cytoplasm, i.e. 78% in group 1 and 36%in group 2.     

Impact of a physical fitness program in a blue-collar workforce

The purpose of this study was to examine the impact of participation in the Wellness--Paths to Health Physical Fitness Program on selected physiological and personal health variables including blood pressure, pulse, body weight, trunk flexibility, cardiovascular endurance, abdominal strength, percent body fat and a cumulative fitness score. The subjects (N = 129) of this study were divided into four levels of adherence to this exercise-based health program. Data analysis examined relationships between adherence levels and changes in the selected physiological and personal health variables across two measures. In addition, data from high-risk participants were analyzed. The results of the study found statistical significant changes in the selected variables between repeated assessment measures. In addition, statistically significant relationships were found between levels of adherence to the program and six of the dependent variables.     

Regression of rat Dunning R-3327-H prostate carcinoma by treatment with targeted cytotoxic analog of luteinizing hormone-releasing hormone AN-207 containing 2-pyrrolinodoxorubicin

The effects of AN-207, a new targeted cytotoxic analog of LH-RH, were evalued in rats bearing hormone-dependent Dunning R-3327-H prostate carcinomas. AN-207 consists of the agonist [D-Lys(6)]LH-RH linked to 2-pyrrolino-doxorubicin, an intensely potent derivative of doxorubicin. In the first experiment, 2-pyrrolinodoxorubicin was administered at a concentration of 50 nmol/kg, as a single drug (AN-201) and as an unconjugated mixture with [D-Lys(6)]LH-RH or conjugated to the carrier [D-Lys(6)]LH-RH (AN-207). Following the second administration of radical AN-201 alone or mixed with the carrier, all rats died with signs of general toxicity, but all animals treated with the conjugate AN-207, survived. After 5 weeks of treatment with a total dose of 150 nmol/kg AN-207, the tumors regressed from an initial volume of 8.35 +/- 1.7 cm(3) to 4.47 +/- 0.8 cm(3), while tumors in the control group measured 17.84 +/- 2.2 cm(3). The therapy with AN-207 also significantly reduced tumor weight and tumor burden. In the second experiment, we compared the efficacy and toxicity of 3 injections of 25 nmol/kg AN-201 or 25 nmol/kg and 50 nmol/kg AN-207. The initial tumor volume in all groups was between 3.9 and 4.5 cm(3). After 5 weeks of therapy, the tumors of rats treated with 50 nmol/kg AN-207 regressed to 2.3 +/- 0.51 cm(3), whereas 25 nmol/kg AN-201 was still toxic in contrast to 25 nmol/kg AN-207, while the reduction in final tumor volume was similar (6.76 +/- 1.4 cm(3) and 6.74 +/- 1 cm(3), respectively), as compared to 15.6 +/- 2.2 cm(3) for untreated animals. High capacity LH-RH receptors were found in the membranes of untreated Dunning tumor specimens, but after treatment with AN-207, they could no longer be detected. This is the first demonstration that the new targeted cytotoxic LH-RH analog AN-207 is an effective antitumor agent. Our work indicates that the cytotoxic analog AN-207 is much less toxic than the antineoplastic radical (AN-201) incorporated, and significantly more active in inhibiting tumor growth. Further development of approaches based on targeted cytotoxic analog AN-207 may lead to major improvements in current palliative therapy of prostate cancer.     

Importance of platelet functions in Alzheimer's disease

The function of platelets of patients with Alzheimer's disease has been characterized. The shape of platelets is more spherical and the initial rate of platelet aggregation caused by different agonists measured in plasma is faster in the case of Alzheimer's disease and senile dementia of the Alzheimer-type than that of other demented patients: multi infarct dementia and probable vascular dementia. Although fast aggregation is characteristic of activated platelets but the Alzheimer platelets are not hypersensitive. The activation of Alzheimer platelets makes the velocity of ADP induced aggregation slower and it is different than the behaviour of normal activated platelets. The shape-associated parameter and the initial rate of 50 microM ADP-induced aggregation of platelets non-activated and activated by cytochrome C are recommended for establishing the diagnosis of Alzheimer's disease and senile dementia of the Alzheimer-type. The evaluation of these parameters has been discussed. The cytochrome C may be useful to normalize the function of Alzheimer platelets in plasma, not only in vitro.     

Economic impact and clinical benefits of pharmacist involvement on surgical wards

A one-year pilot project was performed to assess the economic and clinical benefit of pharmacist involvement on the surgical wards of a 600-bed tertiary care, teaching hospital. A total of 405 recommendations were collected with a physician acceptance rate of 90%. From these recommendations, 1416 patient follow-ups were performed to document outcome. The total documented cost avoidance of the pharmacists' activities was $33,265.58. The total annual drug expenditure for the department of surgery declined by $59,662 representing a 9% decrease over the previous year with the greatest decline involving antimicrobials which decreased by $52,587 compared with the previous year. Most of the cost-avoidance in this area was attributable to antimicrobial selection and dosing adjustment in renal impairment. Pharmacist-directed pharmacokinetic monitoring of aminoglycosides resulted in a clinical success rate of 93.8% for treatment regimens and a 6.2% incidence of nephrotoxicity. Housestaff education aimed at improving prescribing practices were identified and provided for select agents including midazolam, ketorolac, vancomycin and aminoglycosides. As well, select recommendations were documented which illustrated the benefit to patient care of pharmacist involvement. Pharmacist involvement on the surgery services produced both financial and clinical benefits.     

Evaluation of merbarone (NSC 336628) in disseminated malignant melanoma

Merbarone, NSC 336628, is an investigational anticancer drug with activity against experimental animal tumors including melanoma. This paper presents results of a Phase II clinical study of merbarone in patients with biopsy proven stage IV malignant melanoma without prior chemotherapy and with no evidence of CNS involvement. Thirty-five patients with median age 58 (range 27–81), with performance status 0–2 were treated with merbarone 1000 mg/m²/day for five days by intravenous continuous infusion repeated every 3 weeks. All patients (21 males and 14 females) were evaluable for toxicity. Two patients were not evaluable for response having been removed from protocol treatment due to toxicity and received other treatment during the first course of chemotherapy. Among the evaluable patients there was one complete response in a supraclavicular lymph node lasting four months and one partial liver response lasting three months. The remaining thirty-one patients were non-reponders. Of these one had a stable disease lasting 21 months. The overall objective response rate was 6% (2/35) with a 95% confidence interval of 1%–19%. Twenty-six of the 35 patients have died. The estimated median survival of the entire group was 9 months with a 95% confidence interval of six to eleven months. Renal toxicity was dose-limiting and manifested as increasing serum creatinine (54% of patients), proteinuria (51%) and hematuria (9%). One patient experienced grade 4 creatinine increase, proteinuria and acute renal failure. Other toxicities included nausea (71%), vomiting (51%), malaise (23%), weakness (20%), alopecia (17%), diarrhea (17%), anorexia (14%), transaminase (SGOT, SGPT) increase (14%), constipation (14%), alkaline phosphatase or 5nucleotidase increase (9%), and fever (9%). Hematologictoxicity (granulocytopenia, leukopenia, and anemia) was generally mild and infrequent (29%, only one patient had grade 4 granulocytopenia). Overall 9 patients (26%) had at least one grade 3 toxicity. We conclude that merbarone at this dose and schedule has detectable but minimal activity in the treatment of metastatic malignant melanoma and given the significant renal toxicity this schedule does not merit further evaluation in this disease.     

Surgical management of villous and tubulovillous adenomas of the rectum]

One hundred four cases of middle and low rectal villous and tubulovillous adenomas have been operated on with transanal polypectomy (8), transanal endoscopic microsurgery--TEM (80), anterior rectum resection with double stapled straight sigmoideorectosomy (7), and deep rectum resection, bi-directional mucosectomy and hand sutured straight sigmoideoanostomy (9). The option of the authors to remove the tumours in 5 cm to the dentate line are the transanal polypectomy or transanal mucosectomy corresponding to their size. The transanal endoscopic microsurgical technic is recommended to manage the polyps smaller than 4 to 5 cm in the middle rectum. The best radicallity in removal of the circular, extended villous adenomas could be achieved with deep rectum resection, bi-directional mucosectomy and transanal straight, hand sewn sigmoideoanostomy.     

Abdominal actinomycosis presenting as a malignant tumor--report of a case and review of the literature

Actinomyces israelii is a normal inhabitant in the gastrointestinal tract of humans, it rarely causes disease. Abdominal involvement occurs in only 20 percent of all cases and can mimic malignant diseases, tuberculosis and inflammatory bowel disease. A case of a 36 years old female patient with abdominal actinomycosis and review of the literature is reported. Symptoms was presented as an acute abdomen associated with painful epigastric and left subcostal mass. The pathologic process infiltrated the retroperitoneal space simulated sarcoma or lymphoma. Diagnosis was established only at the second laparotomy, when histologic examination of the removed lymph node disclosed actinomycosis. The patient is completely free of symptoms 6 month after the second operation.     

Relationship between clinical and radiological diagnostic criteria for Alzheimer's disease and the extent of neuropathology as reflected by 'stages': a prospective study

The distribution of pathology related to Alzheimer's disease (AD) is not uniform throughout the brain. Sites which have a predilection for the development of Alzheimer-type pathology are the limbic regions and neocortical association areas. The changes in these areas of the brain develop gradually, following a well-determined sequence that allows a pathological staging of the disease process. According to the staging hypothesis, the first pathological alterations develop in the transentorhinal and entorhinal regions. The neurofibrillary pathology then spreads into the hippocampus, but not until the final stages does it affect the neocortex. In this study we analyse the relationship between the pathological stages of AD, according ot the staging hypothesis, and the clinical diagnosis in a prospectively assessed patient group. Prediction of any given pathological stage from the clinical diagnosis was found to be poor. This may be partly due to the fact that additional pathologies can alter the clinical picture and severity of dementia in patients who are only in the initial stages of AD. Nevertheless, the NINCDS-ADRDA clinical criteria had a high sensitivity for detection of AD-related pathology: the 'probable AD' category included 22/38 (57.9%) of those in the late isocortical stage, while the 'possible AD' category included 19/23 (82.6%) of those in the limbic stage. Using proposed neuro-imaging protocols for improved identification of patients with AD-related pathology, we largely identified subjects in whom the extent of pathology had spread to the neocortex.     

PEG-Hemoglobin as a resuscitation solution in the treatment of hypovolemic shock in the anesthetized rat

This study was designed to determine the advantages of using the hemoglobin-based oxygen carrier, polyethylene glycol conjugated bovine hemoglobin (PEG-Hb), as an additive to Ringer's lactate solution (RLS) for the treatment of acute hemorrhage in anesthetized female rats. Different compositions of PEG-Hb and RLS were administered intravenously in a paradigm that provided 30 ml/kg of resuscitation fluid following an episode of 15 min of hypotension. Hypotension was achieved by the removal of blood (1 ml/min) from the femoral vein until the mean arterial pressure was lowered to or below 50 mmHg and subsequently maintained until resuscitation. Short-term cardiovascular assessment showed that resuscitation fluids containing PEG-Hb resulted in higher mean arterial pressure, aortic blood flow, renal blood flow, and less dramatic shifts in arterial base excess and respiratory blood gases than plain RLS. The long-term survival experiment showed lower lactate dehydrogenase, alkaline phosphatase, and serum glutamic pyruvic transaminase levels in most groups resuscitated with solutions containing PEG-Hb, but no differences in survival (100%) were observed. The data suggest that the addition of PEG-Hb to RLS improves its resuscitative effects. Specifically, a solution of 50% RLS:50% PEG-Hb appeared to have the most favorable cardiovascular and metabolic effects in this anesthetized rat hypovolemic shock resuscitation model. Presumably, the improved effects seen with the addition of PEG-Hb were due to its innate plasma expansion and oxygen-delivery capabilities.