Molecular genetics and transfusion management in a child with Bernard Soulier syndrome.

We present a case of Bernard Soulier syndrome in a 9-year-old boy caused by a novel genetic mutation. This child was shown to be homozygous for a single nucleotide deletion (c.1077delG) in the GP1BA gene not previously reported. Clinically, the boy has become refractory to platelet transfusions with both allo-antibodies and iso-antibodies and a massive transfusion requirement for ongoing haemorrhage. We describe the critical role that the blood product transfusion continues to play in the management of Bernard Soulier syndrome and discuss therapeutic options in these patients.     

Brain morphology in first-episode schizophrenic-like psychotic patients: a quantitative magnetic resonance imaging study

Brain morphology was examined using magnetic resonance imaging in 30 first-episode patients with a schizophreniclike psychosis, 15 chronic schizophrenics, and 20 neurological controls. Statistical analyses of computer-generated measurements of regions of interest were controlled for gender, age, social class, and total brain volume. Lateral ventricular size was increased in both first-episode and chronic schizophrenic patients, with greater significance on the left than on the right side. Only the chronic patients, however, had reduced temporal lobe size, which also was greater on the left side. No major correlations of regional brain morphological measurements with cognitive functioning were found, although some measurements of verbal memory were correlated with parahippocampal size. This is a report of a preliminary study that suggests that some morphological brain changes may be present at the time of first treatment for a psychotic illness, whereas others may occur later in the course of illness. Future prospective studies may determine the clinical significance of these changes and whether they progress with the development of illness chronicity.     

Mathematical modeling of nicotine and cotinine as biological markers of environmental tobacco smoke exposure

Computer software developed in our laboratory (CMATRIX) was used to design a physiological pharmacokinetic model of nicotine absorption, distribution, metabolism and excretion in man. The model accommodates inhalation of nicotine from various environmental settings and physiological conditions in man. It was also used to predict pharmacokinetic behavior of cotinine arising from nicotine metabolism. Model-predicted variations in body-fluid nicotine levels confirm that nicotine is not an acceptable quantitative marker of environmental tobacco smoke (ETS) exposure. Though cotinine provides a more stable pattern, predicted interindividual variation suggests the need for specific strict sampling and monitoring guidelines for cotinine to be a reliable quantitative marker.     

Cytomorphometric analysis of vaginal cells during normal cycle, under oral contraceptive therapy or in-vitro fertilization stimulation protocol

A cytomorphometric analysis of superficial vaginal cells inwomen in three groups of different types of hormonal concentrationwas made. There were 15 women in each group. Group I was studiedduring a natural cycle, group II under oral contraceptive therapyand group III during an in-vitro fertilization (IVF) stimulationprotocol. Morphometric parameters were measured on an imageanalyser. The area, perimeter and several form factors weremeasured separately for nuclei and cytoplasm. The nucleus:cytoplasmicratio was also determined. The cytoplasmic area was significantlyreduced in group II and was associated with a statisticallysignificant reduction of the nuclear area. The nucleus:cytoplasmicratio appeared significantly increased in group II and reducedin group III. Low oestradiol impregnation obtained with an oralminidosed contraceptive interfered with vaginal cell maturation.High oestradiol concentrations obtained during IVF protocolsinduced marked nuclear pycnosis but did not induce supra-physiologicalcell enlargement. Maximal cell size is genetically regulatedaccording to Driesch's law of volume invariance and hormonalover-stimulation has no effect on cell size. The nucleus:cytoplasmicratio appears to be a powerful parameter reflecting the oppositeeffects of hormones on cell compartments.     

Arthroscopic acromioplasty. Technique and results

Of forty-four patients who were treated by arthroscopic acromioplasty from July 1984 through August 1986, forty were available for analysis. The average age was 43.2 years, and 86 per cent of them had participated regularly in sports but were disabled due to symptoms of impingement. All patients had had a minimum of six months of non-operative therapy. The final diagnoses, which were based on the findings at arthroscopy and on clinical examination, plain radiographs, and arthrograms, were Stage-II impingement in twenty-four patients, a partial-thickness tear of the rotator cuff in six, and a full-thickness tear of the rotator cuff in ten. The shoulders were scored before the operation and again at follow-up. Preoperatively, thirty-six shoulders were rated as poor and four, as fair. After a minimum follow-up of twelve months (average, seventeen months), the scores had increased in all but one patient. The result was rated good or excellent in twenty-nine (73 per cent) of the forty patients: twenty of the twenty-four who had Stage-II impingement, four of the six who had a partial-thickness tear, and six of the ten who had a full-thickness tear. The over-all average time to return to work was nine days, and the average time to return to sports was 2.4 months. Of the thirty-three patients who had participated in sports, twenty-five (76 per cent) had returned to sports activity at the time of the most recent follow-up. The average time until full recovery was 3.8 months. There were no complications, and, over-all, thirty-eight (92 per cent) of the forty patients were satisfied with the result. In four patients, the result was a failure, and three of the four had a reoperation that relieved the symptoms.     

Characterization and Development of UCI 107, a Primary Human Ovarian Carcinoma Cell Line

We introduce a new epithelial ovarian carcinoma cell line (UCI 107) from a patient with papillary adenocarcinoma of the ovary who had not been previously treated. The growth characteristics, chemosensitivity, tumorgenicity, cytogenetics, antigen expression, and receptor status were examined. A standardized photometric assay was implemented to determine the response to single drug agents including doxorubicin (ADR), cisplatin (CDDP), and Taxol. Tumorgenicity was determined utilizing female athymic mice implanted either subcutaneously (sc) or intraperitoneally (ip) with 1 × 10⁷ UCI 107 cells. UCI 107 cells grow rapidly in culture with lag phase of approximately 48 hr, population doubling time of 24-36 hr, and saturation density of 4.8 × 10⁵ cells/cm². The 50% inhibitory concentration values for the chemotherapeutic agents were 0.170, 0.029, and 0.330 μM for ADR, Taxol, and CDDP, respectively. Nude mice produced ip tumors within 15 days, resulting in death from carcinomatosis 40-45 days postimplantation. Subcutaneous tumor nodules (100 mm³ were observed in nude mice 12-13 days post-tumor implantation reaching a maximum tumor volume of approximately 10,000 mm³ by Day 30. The cytogenetic composite karyotype is as follows: 46, X, der (X) t (X;7) (p11;q22), inv dup (1) (q12;q32), t (6;6;11;22) (p21.3;q16;q23.3;q13.3), del (13) (q14.1). The cell line expresses progesterone receptor, increased levels of p53 protein, and cytokeratins. It does not appear to express Her-2/neu protein, estrogen receptor, nor the CA 125 tumor marker. In conclusion, UCI 107 displays unique cellular properties which make it an attractive model for the study of ovarian cancer.     

Origins of heterogeneous ovarian carcinomas. A molecular cytogenetic analysis of histologically benign, low malignant potential, and fully malignant components.

It is unclear whether ovarian carcinomas develop from malignant transformation of benign precursors or whether they arise de novo. Thus, histologically benign or low malignant potential components found in heterogeneous ovarian carcinomas may be remnants of pre-existing lesions that progressed to malignancy or, alternatively, elements that arose independently (de novo). In a third possible interpretation, they represent areas of malignant epithelium that matured. We evaluated clonal relationships of histological components in 10 heterogeneous ovarian carcinomas using fluorescence in situ hybridization and confocal microscopy. Detailed analysis of aneuploidy for chromosomes 8, 12, and 17 on intact paraffin sections revealed that two tumors were aneuploid in all components, two lacked abnormalities in benign-appearing components, and one lacked aneuploidy in both histologically benign and low malignant potential components. Histological appearance was significantly related to aneuploidy (P < 0.05). The distribution of aneuploidy among tumor components strongly supports the tumor progression theory and demonstrates that the de novo hypothesis is highly unlikely (P < 0.001). Results also indicate that benign-appearing components in heterogeneous ovarian carcinomas do not represent maturation of malignant tissue and suggest that some benign tumors that become cancerous may have genetic aberrations that predispose them to malignant transformation.     

Black/white comparisons of deaths preventable by medical intervention: United States and the District of Columbia 1980-1986

Blacks in the US experience increased mortality (1113 versus 745 per 100,000 males; 631 versus 411 per 100,000 females) and decreased life expectancy (63.7 years versus 70.7 years for males; 72.3 years versus 78.1 years for females); compared to Whites. In an effort to determine if the excess mortality among Black Americans might be explained by differences in access or quality of health care services, we performed a race-specific analysis of conditions for which mortality is largely avoidable given timely and appropriate medical care. Using methodology proposed by Rutstein and Charlton, mortality due to 12 causes was evaluated including tuberculosis, cervical cancer, Hodgkin's disease, rheumatic heart disease, hypertensive heart disease, acute respiratory disease, pneumonia and bronchitis, influenza, asthma, appendicitis, hernias and cholecystitis. In the US, during 1980 to 1986, an average of 17,366 deaths and 286,813 years of potential life (YPLL) before age 65 were lost each year due to all 12 sentinel causes combined. Of these causes, hypertensive heart disease, pneumonia and bronchitis, cervical cancer and asthma accounted for the greatest number of deaths. The mortality rate for all 12 causes combined among Blacks was 4.5 times that of Whites. The highest relative rates among Blacks compared to Whites were observed for tuberculosis, hypertensive heart disease and asthma. The overall mortality rate in the District of Columbia for the selected causes was 3.7 times the national rate. Compared to national rates, statistically significant elevated rates in the District were observed for tuberculosis, hypertensive heart disease and pneumonia and bronchitis.(ABSTRACT TRUNCATED AT 250 WORDS)