A challenging case of hypercapnic respiratory failure during pregnancy.

We describe a 40-year-old female who presented with progressive breathlessness and hypercapnic respiratory failure during pregnancy secondary to undiagnosed muscle-specific kinase myasthenia gravis. Her presentation was progressive and protracted, having over five contacts with healthcare professionals over nine months, many of these predating her pregnancy. Her atypical presentation for myasthenia with minimal limb weakness led to consideration of other causes of hypercapnic respiratory failure. Once diagnosed, she was treated with intravenous immunoglobulin and non-invasive ventilation. She gave birth to a pre-term infant by planned caesarean section. Her insidious presentation and the progressive nature of her breathlessness were unusual and our report highlights the predominant involvement of respiratory muscles in muscle-specific kinase myasthenia. Her pregnancy may have further delayed her diagnosis due the attribution of some symptoms to normal pregnancy. Early recognition and treatment of myasthenia gravis are important to prevent life-threatening complications.

Relationships between MRI fat distributions and sleep apnea and obesity hypoventilation syndrome in very obese patients.

PURPOSE: Obesity is associated with both obstructive sleep apnea (OSA) and obesity hypoventilation. Differences in adipose tissue distribution are thought to underlie the development of both OSA and hypoventilation. We explored the relationships between the distribution of upper airway, neck, chest, abdominal and muscle fat in very obese individuals. METHODS: We conducted a cross-sectional cohort study of individuals presenting to a tertiary sleep clinic or for assessment for bariatric surgery. Individuals underwent magnetic resonance (MR) imaging of their upper airway, neck, chest, abdomen and thighs; respiratory polygraphy; 1 week of autotitrating CPAP; and morning arterial blood gas to determine carbon dioxide partial pressure and base excess. RESULTS: Fifty-three individuals were included, with mean age of 51.6 ± 8.4 years and mean BMI of 44.3 ± 7.9 kg/m2; there were 27 males (51%). Soft palate, tongue and lateral wall volumes were significantly associated with the AHI in univariable analyses (p < 0.001). Gender was a significant confounder in these associations. No significant associations were found between MRI measures of adiposity and hypoventilation. CONCLUSIONS: In very obese individuals, our results indicate that increased volumes of upper airway structures are associated with increased severity of OSA, as previously reported in less obese individuals. Increasingly large upper airway structures that reduce pharyngeal lumen size are likely to lead to OSA by increasing the collapsibility of the upper airway. However, we did not show any significant association between regional fat distribution and propensity for hypoventilation, in this population.

Cardiovascular event rates in the MOSAIC trial: 2-year follow-up data.

The Multicentre Obstructive Sleep Apnoea Intervention Cardiovascular (MOSAIC) trial investigated the effect of continuous positive airway pressure (CPAP) on both sleepiness and predicted cardiovascular risk over 6 months in minimally symptomatic patients with obstructive sleep apnoea. Although there was clear benefit in terms of Epworth Sleepiness Score, there was no improvement in blood pressure and predicted vascular risk score. In order to calculate the required size of future trials, with real vascular events as the endpoint, the rate of such events in this population is needed. 188 patients from the original trial were followed for 2 years. The overall number of new vascular events over the 2 years was 25, and all-cause mortality was 4. There was a weak statistically significant reduction in vascular events in the CPAP group (p=0.049). Large-scale randomised trials are needed to determine if CPAP causes a real reduction in vascular events in minimally symptomatic patients. Based on our figures, future trials of CPAP versus no treatment would need to randomise approximately 2540 patients to not miss a real reduction in vascular events and over 6000 for mortality.

The effects of immersion and exercise on prolactin during pregnancy.

Prolactin is an important hormone during pregnancy, affecting mother, fetus, and amniotic fluid volume. Immersion is known to affect prolactin levels significantly. To determine the effect of immersion and exercise on the prolactin response during pregnancy, we examined serum prolactin levels at 15, 25, and 35 weeks' gestation and 10 weeks post partum. Twelve women completed 20 min land rest, 20 min immersion in 30 degrees C water to the xiphoid, and 20 min exercise in the water at 60% VO2max. Resting prolactin levels were 1.91 +/- 0.32, 4.55 +/- 0.5, and 5.85 +/- 0.27 nmol.l-1 +/- standard error of the mean at 15, 25, and 35 weeks' gestation, respectively. Postpartum lactating women had a resting mean prolactin level of 3.95 +/- 1.6 versus 0.22 +/- 0.4 nmol.l-1 in non-lactating women. Prolactin levels declined significantly during immersion even after correction for dilution by plasma volume shifts. The immersion response was inversely related to the duration of pregnancy with 29%, 22%, and 12% drops during 15-, 25- and 35-week trials, respectively. Compared to rest, exercise prolactin levels remained depressed during the 15th and 25th week trials. We hypothesize that immersion in water caused prolactin levels to decline.

The effects of isocarboxazid on blood pressure and pulse.

In a fixed-dose inpatient study, isocarboxazid produced a dose-related lowering of systolic blood pressure at weeks 2 and 4. Systolic blood pressure was also lowered by the drug in a placebo-controlled outpatient study. The magnitude of these reductions was considerable, reaching an average of 14.6 mm in inpatients who received a 50-mg dose, and 18.7 mm in outpatients. There was no evidence for a dose-related orthostatic effect, and greater orthostasis relative to placebo was found only at week 3 in the outpatient study. Significant bradycardia was produced by isocarboxazid in outpatients at weeks 2, 3, and 4 relative to placebo, but no dose-related effect was found among inpatients. Inpatients with a baseline systolic orthostatic drop of greater than or equal to 10 mm showed a significantly better response to isocarboxazid than did those with an orthostasis of less than 10 mm. The theoretical significance of these findings is discussed.

The Montgomery-Asberg Depression Scale: reliability and validity.

The Montgomery-Asberg Depression Scale was evaluated in 44 depressed inpatients. All items of the scale occurred frequently in the sample; the scale exhibited construct validity (internal homogeneity) and concurrent validity relative to the Hamilton Depression Scale and the concepts of endogenous and nonendogenous depression. Sleep disturbance, reduced appetite, and suicidal thoughts, correlated poorly with the remainder of the scale. Reasons for this finding are discussed. Inter-rater reliability was demonstrated between a psychiatrist and a nurse on individual item and total scale scores.

Diagnostic significance of vegetative symptoms in depression.

The diagnostic importance of vegetative symptoms for melancholia was examined through DSM-III, the Newcastle Scale, and Extracted Criteria for melancholia. Statistically significant differences were diagnostically unimpressive in the case of DSM-III and the Newcastle criteria. With the Extracted Criteria, initial insomnia, early waking, anorexia, weight loss, loss of libido, and worsened mood in the morning were all significantly more common in melancholia than in non-melancholic depression, while increased appetite was more common in non-melancholia. Only diurnal variation of mood (worse in the morning) showed predictive value for melancholia; whereas the other traditional vegetative symptoms (disturbed sleep, weight, and libido) did not. Increased appetite and diurnal variation of mood (worse in the evening) were predictive for non-melancholia.

An evaluation of two doses of isocarboxazid in depression.

Two fixed doses of isocarboxazid were studied over a 4-week period in depressed in-patients. Thirty-five patients completed treatment, 20 of whom received 30 mg isocarboxazid per day, and 15 of whom received 50 mg isocarboxazid per day. No overall difference between the two doses was observed. When patients were subdivided into melancholia/endogenous depression or non-melancholia/non-endogenous depression, the higher dose exerted significantly greater antidepressant effects in the latter groups. Diagnostic type is considered to be an important variable in studies of dose-effect relationships with antidepressant drugs. The side effects of isocarboxazid at the two doses studied did not differ materially, although there was a suggestion of greater anticholinergic effect at 50 mg.

Atypical depression.

The term atypical depression generally indicates either depression accompanied by severe anxiety (type A) or by atypical vegetative symptoms, ie, increased appetite, weight, sleep, or libido (type V). Early age at onset, predominance in women, outpatient status, mild intensity, rarity of attempted suicide, nonbipolarity, nonendogenicity, and minimal psychomotor change are common to both types. Some types of bipolar depression may be considered as atypical if accompanied by reversed vegetative change. Monoamine oxidase inhibitors are more effective than placebo in treating atypical depression, but their reported superiority to tricyclic antidepressants awaits confirmation, for which the development of appropriate operational criteria would be helpful. Atypical depression is a term that covers several types of depressive disorder and can, for the most part, be better defined using the standard nomenclature.

A comparison of phenelzine and imipramine in depressed inpatients.

Phenelzine and imipramine were compared double-blind, in 43 depressed inpatients. A placebo week preceded drug treatment; this allowed early identification of placebo responders who did not therefore enter the study. After three weeks treatment, the two drugs were equally effective on Hamilton, Beck and SCL-90 measures of depression and anxiety. On the the SCL-90 scales of hostility and paranoia imipramine was more effective; in some patients phenelzine was associated with increased hostility. Measurement of MAO inhibition and plasma tricyclic levels indicated that adequate doses were generally used - (mean 81 mg/day phenelzine and 144 mg/day imipramine).

MAO inhibition and control of anxiety following amitriptyline therapy. A pilot study.

In a pilot study, 32 patients with mixed states of anxiety, depression, somatization and panic received amitriptyline for 4 weeks, the dose ranging from 50 to 300 mg/day. Steady-state plasma levels of the drug and activity of platelet monoamine oxidase were measured after 4 weeks. Clinical change was rated, using the SCL-90. Amitriptyline produced a small but significant inhibition of platelet monoamine oxidase activity (range 1.4--82%). A significant positive correlation was noted between MAO inhibition and improvement on somatization, and psychological and panic-phobic components of anxiety, but not for depression. No significant correlations were observed between improvement and combined or separate ami- + nortriptyline plasma levels.

Platelet monoamine oxidase activity and the classification of depression.

An attempt was made to compare platelet monoamine oxidase (MAO) activity in descriptively based types of nonbipolar depression. Platelet MAO activity was significantly higher in depression secondary to chronic anxiety, compared with primary unipolar depression and depression secondary to borderline personality, and in women compared with men. No significant differences were observed between endogenous-nonendogenous, delusional-nondelusional, psychomotor states, or different age groups.

A comparison of inpatients with primary unipolar depression and depression secondary to anxiety.

Retrospective comparisons between primary unipolar depression and depression secondary to anxiety in 65 inpatients revealed a number of differences. Secondary depression was associated with a significantly higher incidence of neurotic traits in childhood, chronic unhappiness, and unsupportive family. Tricyclic antidepressants and ECT were both more effective in primary depression, and some secondary depressives became worse on ECt. When primary depression was sub-divided into familial, nonfamilial and spectrum types, the greatest differences were noted between familial and secondary depressions. In the former group a more stable life style was noted. Secondary and spectrum types differed on only two variables and several similarities were noted. Platelet monoamine oxidase activity was significantly higher in secondary depression.

Catechol-O-methyltransferase activity and classification of depression.

Red blood cell catechol-O-methyltransferase (COMT) activity was compared across different depressive diagnoses. In a sample of 88 depressed inpatients, using defined criteria, no difference was found in respect of enzyme activity and the following categories: primary, secondary, delusional, nondelusional, endogenous, nonendogenous (neurotic), characterological depressions. COMT did not vary with age or sex. A significant increase in COMT activity was noted in agitated, depressed males, as compared to other groups.