Posttraumatic stress disorder among female Vietnam veterans: a causal model of etiology.

OBJECTIVES: The Vietnam and Persian Gulf wars have awakened people to the realization that military service can be traumatizing for women as well as men. This study investigated the etiological roles of both war and sexual trauma in the development of chronic posttraumatic stress disorder among female Vietnam veterans. METHODS: Data from the National Vietnam Veterans Readjustment Study for 396 Vietnam theater women and 250 Vietnam era women were analyzed with structural equation modeling. RESULTS: An etiological model with highly satisfactory fit and parsimony was developed. Exposure to war trauma contributed to the probability of posttraumatic stress disorder in theater women, as did sexual trauma in both theater and era women. Lack of social support at the time of homecoming acted as a powerful mediator of trauma for both groups of women. CONCLUSIONS: Within the constraints and assumptions of causal modeling, there is evidence that both war trauma and sexual trauma are powerful contributors to the development of posttraumatic stress disorder among female Vietnam veterans.

Restoration of half the normal dystrophin sequence in a double-deletion Duchenne muscular dystrophy family.

Two male cousins with Duchenne muscular dystrophy were found to have different maternal dystrophin gene haplotypes and different deletion mutations. One propositus showed two noncontiguous deletions--one in the 5', proximal deletional hotspot region, and the other in the 3', more distal deletional hotspot region. The second propositus showed only the 5' deletion. Using multiple fluorescent exon dosage and fluorescent multiplex CA repeat linkage analyses, we show that the mother of each propositus carries both deletions on the same grandmaternal X chromosome. This paradox is explained by a single recombinational event between the 2 deleted regions of one of the carrier's dystrophin genes, giving rise to a son with a partially "repaired" gene retaining only the 5' deletion.

Assessment of alcoholism among dually diagnosed psychiatric inpatients.

Alcohol is an increasingly abused substance among psychiatric inpatients, and the extent to which alcohol dependence history is documented and the alcoholism subsequently treated is a compelling issue. This study is a retrospective review of the extent to which alcohol dependence history was obtained, and if applicable, whether a diagnosis and/or treatment plan were made, for acute psychiatric inpatients. For these purposes, an original instrument was constructed. Our results indicate that the predominant focus for acute inpatients is on diagnostic assessment of the severity of the alcohol problem, reflecting the need to deal with those issues requiring the most immediate attention. For patients with schizophrenia, attention to alcoholism diagnosis and treatment was less than that for nonschizophrenic patients. The implications of these findings are discussed with reference to the evaluation and treatment of dually diagnosed patients, along with further directions for research.

Fluorescent multiplex linkage analysis and carrier detection for Duchenne/Becker muscular dystrophy.

We have developed a fast and accurate PCR-based linkage and carrier detection protocol for families of Duchenne muscular dystrophy (DMD)/Becker muscular dystrophy (BMD) patients with or without detectable deletions of the dystrophin gene, using fluorescent PCR products analyzed on an automated sequencer. When a deletion is found in the affected male DMD/BMD patient by standard multiplex PCR, fluorescently labeled primers specific for the deleted and nondeleted exon(s) are used to amplify the DNA of at-risk female relatives by using multiplex PCR at low cycle number (20 cycles). The products are then quantitatively analyzed on an automatic sequencer to determine whether they are heterozygous for the deletion and thus are carriers. As a confirmation of the deletion data, and in cases in which a deletion is not found in the proband, fluorescent multiplex PCR linkage is done by using four previously described polymorphic dinucleotide sequences. The four (CA)n repeats are located throughout the dystrophin gene, making the analysis highly informative and accurate. We present the successful application of this protocol in families who proved refractory to more traditional analyses.

Sequence and genomic structure of the human adult skeletal muscle sodium channel alpha subunit gene on 17q.

The amino acid sequence of the sodium channel alpha subunit from adult human skeletal muscle has been deduced by cross-species PCR-mediated cloning and sequencing of the cDNA. The protein consists of 1836 amino acid residues. The amino acid sequence shows 93% identity to the alpha subunit from rat adult skeletal muscle and 70% identity to the alpha subunit from other mammalian tissues. A 500 kb YAC clone containing the complete coding sequence and two overlapping lambda clones covering 68% of the cDNA were used to estimate the gene size at 35 kb. The YAC clone proved crucial for gene structure studies as the high conservation between ion channel genes made hybridization studies with total genomic DNA difficult. Our results provide valuable information for the study of periodic paralysis and paramyotonia congenita, two inherited neurological disorders which are caused by point mutations within this gene.

A Met-to-Val mutation in the skeletal muscle Na+ channel alpha-subunit in hyperkalaemic periodic paralysis.

HYPERKALAEMIC periodic paralysis (HYPP) is an autosomal dominant disease that results in episodic electrical inexcitability and paralysis of skeletal muscle. Electrophysiological data indicate that tetrodotoxin-sensitive sodium channels from muscle cells of HYPP-affected individuals show abnormal inactivation. Genetic analysis of nine HYPP families has shown tight linkage between the adult skeletal muscle sodium channel alpha-subunit gene on chromosome 17q and the disease (lod score, z = 24; recombination frequency 0 = 0), strongly suggesting that mutations of the alpha-subunit gene cause HYPP. We sequenced the alpha-subunit coding region isolated from muscle biopsies from affected (familial HYPP) and control individuals by cross-species polymerase chain reaction-mediated complementary DNA cloning. We have identified an A----G substitution in the patient's messenger RNA that causes a Met----Val change in a highly conserved region of the alpha-subunit, predicted to be in a transmembrane domain. This same change was found in a sporadic case of HYPP as a new mutation. We have therefore discovered a voltage-gated channel mutation responsible for a human genetic disease.

A biopsychosocial treatment approach to the management of diabetes mellitus.

The relationship among recent life stress, social support, a patient's locus of control, and the control of blood glucose is evaluated in persons with diabetes mellitus, using objective measures of these psychosocial variables. Short-term [fasting blood sugar (FBS)] and long-term [glycosylated hemoglobin (Hgb A-1C)] control measures are taken at two points in time in order to evaluate the effects of the psychosocial variables on change in diabetes control. For life events, a significant positive association was found between the number of recent life events and blood glucose control. Decrease in social support predicted a worsening of longer-term (Hgb A-1C) control over time. An external locus of control within the patient was associated both with poor short-term control at time one and prediction of poorer long-term control over time. The implications of these findings are discussed in support of a biopsychosocial approach to the management of diabetes mellitus.

Attitudes of mental health professionals toward alcoholism recognition and treatment.

The attitudes of 100 urban mental health professionals toward alcoholism diagnosis and treatment were assessed using a 23-item questionnaire. A significant number of those sampled, physicians more than other professional groups, looked upon alcoholism as a disease in its own right. Physicians, attendings more than residents, subscribed to a more medical history-taking model. While the majority of those surveyed would advise complete sobriety, a large number would not. Likewise, despite a large percentage of our sample who indicated familiarity with alcohol-related concepts, a significant number did not. Referral to Alcoholics Anonymous was highly endorsed by those advocating sobriety. The meaning of these findings is discussed in relation to the marked improvement noted in professionals' attitudes toward alcoholic patients. Based on these findings, methods of further improving the clinician's awareness of alcoholism are considered.

Plasmid instability kinetics of the yeast S288C pUCKm8 [cir+] in non-selective and selective media.

Plasmid loss kinetics for Saccharomyces cerevisiae transformed with the 2-mum DNA-based-plasmid pUCKm8 were measured in nonselective and selective media. The plasmid pUCKm8 gives the organism two new phenotypes: resistance to the wide spectrum antibiotic G418 sulfate, and the ability to produce the enzyme, beta-lactamase. Plasmid stability was determined using the production of beta-lactamase as a marker. The effect of G418 on the growth rates of all organisms present in the culture and on plasmid stability was also determined. Mathematical models describing plasmid loss kinetics during exponential growth for both nonselective and selective conditions are used to simulate the experimental data. In nonselective medium, over 80% of the cells still exhibited the desired phenotype after 50 doublings. In medium containing G418, improvements in plasmid stability were only marginal due to the appearance of antibiotic-resistant cells.

A biopsychosocial approach to the management of the diabetic patient.

Among the psychosocial variables to be considered by the primary care physician in dealing with a diabetic patient are the effects of stressful life events, social support, and the patient's locus of control. Literature relevant to each of these is explored. A practical approach is discussed for the primary care doctor to consider in utilizing these psychosocial variables in diabetes management.

The role of recent life events and social support in the control of diabetes mellitus. A pilot study.

This study evaluated objectively the relationship between recent life events, social support systems, and blood glucose control in diabetic patients using both short-term [fasting blood sugar (FBS)] and long-term [glycosylated hemoglobin (Hgb A-1C)] measures of control. We found that a higher number of life events was associated with a higher percentage of abnormal FBS and Hgb A-1C results, and that improved social support was associated with a smaller percentage of abnormal Hgb A-1C scores. These pilot findings are discussed in connection with a biopsychosocial approach to the understanding and management of diabetes mellitus.

A supportive care clinic: maintaining the chronic psychiatric patient.

A comprehensive investigation into the social support networks of a group of chronic psychiatric patients attending a Supportive Care Clinic was conducted. The results suggest that these patients, while exhibiting weaker support systems than the general population, do have a significant amount of personal support in addition to that received from the treatment center. Furthermore, they perceive the "support" aspect of the Clinic as the most helpful feature as compared to personal growth or medication. The results of these findings are discussed in terms of their practical utility for the ambulatory care of chronic psychiatric patients.

Agoraphobia: a multimodal treatment approach.

A female patient with agoraphobia is presented to demonstrate the need for maximal flexibility in designing a treatment program for the agoraphobic patient. This patient required a multimodal approach utilizing pharmacotherapy, marital psychotherapy, and individual psychotherapy, alone and in combination. The paper looks specifically at nodal decision points in treatment at which reassessment was necessary and changes in psychotherapeutic intervention were made. The importance and implications of involving the patient's significant other in treatment are explored with respect to the outcomes such involvement may have on the treatment. A review of the literature on treatments for agoraphobia highlights the conclusion reached, that the agoraphobic patient presents with a biopsychosocial problem which frequently requires the clinician to combine several treatment modalities.